ergoline and Hypertension

The endogenous catecholamine dopamine lowers blood pressure by acting on two receptor subtypes: dopamine 1 and dopamine 2. Dopamine 1 receptors subserve vasodilation, especially in the renal, coronary, mesenteric, and cerebral vascular beds. Dopamine 2 receptors have been located at the endings of postganglionic sympathetic nerves and, when activated, inhibit norepinephrine release. Inhibition of emesis and inhibition of prolactin release also appear to be dopamine 2-mediated phenomena. The receptor subtypes have been classified by differences in chemical structure of agonists and by specific antagonists. Dopamine also acts on beta 1 receptors to stimulate the heart and alpha 1 and alpha 2 receptors to cause vasoconstriction. Alpha adrenergic activity and lack of oral availability limit the use of dopamine in the treatment of hypertension. However, studies with the selective dopamine 1 agonist, fenoldopam, and dopamine 2 agonists such as LY 141865 and bromocriptine, indicate that agonists of both receptor subtypes can lower blood pressure in experimental animals and in hypertensive patients. Initial use of dopamine agonists in the treatment of hypertension and its possible involvement in the etiology and maintenance of hypertension are discussed.

Topics: Animals; Benzazepines; Blood Pressure; Bromocriptine; Domperidone; Dopamine; Ergolines; Fenoldopam; Humans; Hypertension; Levodopa; Quinpirole; Receptors, Adrenergic, alpha; Receptors, Adrenergic, beta; Receptors, Dopamine; Receptors, Dopamine D1; Receptors, Dopamine D2; Vasoconstriction; Vasodilation

Relatively selective dopamine receptor agonists, like bromocriptine, lergotrile, pergolide and N,N-di-n-propyl-dopamine, lower arterial pressure in conscious spontaneously hypertensive rats and in several anesthetized animal preparations. This effect has been attributed to stimulation of dopamine receptors since it can be specifically antagonized by several dopamine receptor blocking agents (domperidone, haloperidol, pimozide, sulpiride). The two main mechanisms which can theoretically intervene in the antihypertensive effects of dopamine agonists are direct smooth muscle relaxation mediated by stimulation of post junctional DA1-dopamine receptors and the reduction of the neural release of norepinephrine resulting from activation of of DA2-dopamine receptors on ganglionic bodies or sympathetic nerve terminals. Other accessory mechanisms of undoubted interest might be a natriuretic effect or a decrease of aldosterone release. On the basis of the presently available pharmacological results in experimental animals, it is not unreasonable to advance the hypothesis that agonists of DA1- and DA2-dopamine receptors produce cardiovascular changes most compatible with an antihypertensive activity being due to a fall in peripheral resistance. However, before any of these compounds can become of therapeutic interest further research in this field is necessary to explore whether it is possible to minimize or even entirely avoid certain unwanted effects (vomiting, nausea, endocrinological alterations) that appear to be intimately associated particularly with those agents stimulating the DA2-dopamine receptors subtype. A more thorough pharmacological characterization of human dopamine receptors would be useful to provide an insight into whether novel chemical approaches can solve some of these problems. Finally, the ideal profits of future dopamine receptor agonists aimed at the treatment of elevated arterial pressure is discussed.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Clonidine; Ergolines; Heart Rate; Hypertension; Models, Biological; Pergolide; Rats; Receptors, Dopamine; Vascular Resistance

Cianergoline is a new dopaminergic agonist with a predominant cardiovascular action. Its effects on blood pressure, the renin-angiotensin-aldosterone axis, the sympathetic nervous system and lipid metabolism were assessed in 20 patients with benign essential hypertension. Cianergoline given in increasing doses for 4 weeks (maximum daily dose 12 +/- 2 mg (SD)) and placebo both caused a slight decrease in arterial pressure, (from 159/104 to 152/98 mm Hg and from 154/104 to 149/103 mm, respectively; difference not significant). Supine and upright plasma renin activity, plasma aldosterone, norepinephrine, epinephrine and dopamine levels, urinary catecholamine excretion rates as well as serum prolactin, low and high density cholesterol and triglyceride concentrations were not changed after cianergoline or placebo. Total serum cholesterol and triglyceride levels decreased significantly after placebo, but were unchanged after cianergoline. 3 out of 10 patients in the cianergoline group complained of nausea. The findings indicate that the new dopaminergic agonist cianergoline exerts only a mild blood pressure lowering effect in patients with essential hypertension and does not modify the release of prolactin, lipid metabolism or the basal activity or postural responsiveness of the renin-angiotensin-aldosterone axis and of the sympathetic nervous system.

Topics: Adult; Aged; Blood Pressure; Ergolines; Female; Humans; Hypertension; Male; Middle Aged; Receptors, Dopamine; Renin-Angiotensin System; Sympathetic Nervous System

The tolerance and anti-hypertensive activity of nicergoline, an alpha-adrenoceptor blocking agent, were studied in 28 hypertensive subjects older than 65 years (mean age: 84 years). The trial was conducted double-blind: 14 subjects were given nicergoline 30 mg/day divided into 6 doses ("lyocs"), and 14 subjects received a placebo identical in appearance with the drug. A mean decrease of 34 mm Hg in systolic arterial pressure (p < 0.001) and of 16 mm Hg in diastolic arterial pressure (p < 0.001) was observed in subjects under nicergoline. The corresponding changes in blood pressure (-12 and -7.9 mm Hg respectively) in subjects under placebo were not significant. No side-effect requiring discontinuation of treatment was encountered. The remarkable effectiveness and tolerance of nicergoline make it a highly suitable agent for the treatment of hypertension in elderly people.

Topics: Aged; Clinical Trials as Topic; Double-Blind Method; Ergolines; Female; Humans; Hypertension; Male; Nicergoline

An examination was carried out on the efficacy of 10-methoxy-1,6-diemethyl-ergoline-8 beta-methanol-(5-bromonicotinate) (nicergoline, Sermion) on the symptoms of functional side effects of arterial hypertension and chronic circulatory insufficiency as regards the psychomotoric activity and the relational activity; 359 patients suffering from crebrovascular insufficiency were included in the study. The compound was applied in a daily dose of 10 mg i. m. for 5 days and then in a daily dose of 15 mg orally for 1 month. In the entire symptom complex of cerebro-vascular insufficiency a positive effect of nicergoline could be observed; the results of all clinical criteria and their therapeutic relevance are discussed.

Topics: Adult; Aged; Cerebrovascular Disorders; Chronic Disease; Clinical Trials as Topic; Ergolines; Female; Humans; Hypertension; Male; Middle Aged; Nicergoline

Cushing disease (CD) results from excessive exposure to glucocorticoids caused by an adrenocorticotropic hormone-secreting pituitary tumor. Inadequately treated CD is associated with significant morbidity and elevated mortality. Multicenter data on CD patients treated in routine clinical practice are needed to assess treatment outcomes in this rare disorder. The study purpose was to describe the burden of illness and treatment outcomes for CD patients.. Eight pituitary centers in four U.S. regions participated in this multicenter retrospective chart review study. Subjects were CD patients diagnosed at ≥18 years of age within the past 20 years. Descriptive statistical analyses were conducted to examine presenting signs, symptoms, comorbidities, and treatment outcomes.. Of 230 patients, 79% were female (median age at diagnosis, 39 years; range, 18 to 78 years). Length of follow-up was 0 to 27.5 years (median, 1.9 years). Pituitary adenomas were 0 to 51 mm. The most common presenting comorbidities included hypertension (67.3%), polycystic ovary syndrome (43.5%), and hyperlipidemia (41.5%). Biochemical control was achieved with initial pituitary surgery in 41.4% patients (91 of 220), not achieved in 50.0% of patients (110 of 220), and undetermined in 8.6% of patients (19 of 220). At the end of follow-up, control had been achieved with a variety of treatment methods in 49.1% of patients (110 of 224), not achieved in 29.9% of patients (67 of 224), and undetermined in 21.0% of patients (47 of 224).. Despite multiple treatments, at the end of follow-up, biochemical control was still not achieved in up to 30% of patients. These multicenter data demonstrate that in routine clinical practice, initial and long-term control is not achieved in a substantial number of patients with CD.. BLA = bilateral adrenalectomy CD = Cushing disease CS = Cushing syndrome eCRF = electronic case report form MRI = magnetic resonance imaging PCOS = polycystic ovary syndrome.

Topics: 14-alpha Demethylase Inhibitors; ACTH-Secreting Pituitary Adenoma; Adenoma; Adolescent; Adrenalectomy; Adult; Aged; Antineoplastic Agents; Cabergoline; Comorbidity; Enzyme Inhibitors; Ergolines; Female; Follow-Up Studies; Hirsutism; Hormone Antagonists; Hormones; Humans; Hyperlipidemias; Hypertension; Hypoglycemic Agents; Ketoconazole; Male; Metyrapone; Middle Aged; Mifepristone; Muscle Weakness; Muscular Atrophy; Neurosurgical Procedures; Obesity, Abdominal; Pituitary ACTH Hypersecretion; Pituitary Irradiation; Polycystic Ovary Syndrome; Retrospective Studies; Rosiglitazone; Somatostatin; Striae Distensae; Thiazolidinediones; Treatment Outcome; Tumor Burden; Young Adult

Cushing's disease (CD) is often accompanied by hypertension. CD can be treated surgically and, given the expression of somatostatin subtype 5 and dopamine 2 receptors by corticotroph pituitary adenomas, pharmacologically. Indeed, we recently observed that stepwise medical combination therapy with the somatostatin-analog pasireotide, the dopamine-agonist cabergoline, and ketoconazole (which directly suppresses steroidogenesis) biochemically controlled CD patients and lowered their blood pressure after 80 days. Glucocorticoids (GC) modulate the renin-angiotensin-aldosterone system (RAAS) among others by increasing hepatic angiotensinogen expression and stimulating mineralocorticoid receptors (MR). This study therefore evaluated plasma RAAS components in CD patients before and after drug therapy. In addition, we studied whether cabergoline/pasireotide have direct relaxant effects in angiotensin II (Ang II)-constricted iliac arteries of spontaneously hypertensive rats, with and without concomitant GR/MR stimulation with dexamethasone or hydrocortisone.. Baseline concentrations of angiotensinogen were elevated, while renin and aldosterone were low and suppressed, respectively, even in patients treated with RAAS-blockers. This pattern did not change after 80 days of treatment, despite blood pressure normalization, nor after 4 years of remission. In the presence of dexamethasone, pasireotide inhibited Ang II-mediated vasoconstriction.. The low plasma renin concentrations, even under RAAS blockade, in CD may be the consequence of increased GC-mediated MR stimulation and/or the elevated angiotensinogen levels in such patients. The lack of change in RAAS-parameters despite blood pressure and cortisol normalization suggests persisting consequences of long-term exposure to cortisol excess. Finally, pasireotide may have a direct vasodilating effect contributing to blood pressure lowering.

Topics: Adult; Aged; Aldosterone; Angiotensinogen; Animals; Cabergoline; Ergolines; Female; Humans; Hypertension; Iliac Artery; In Vitro Techniques; Male; Middle Aged; Pituitary ACTH Hypersecretion; Rats; Renin; Renin-Angiotensin System; Somatostatin; Vasoconstriction

Cabergoline is a long-acting dopamine receptor agonist used for treatment of patients with uncured Cushing's disease (CD) and, as a first-line treatment, was used in only limited numbers of patients. This report presents two adolescent boys with CD who were treated with cabergoline. Two adolescent boys with clinical and laboratory findings of CD are presented. No pituitary adenoma was detected by radiological investigation in either patient. Adrenocorticotropic hormone (ACTH) hypersecretion and lateralization was found by inferior petrosal sinus sampling in both patients. The initial cabergoline dose was 1mg/week and was adjusted up to 1.5 mg/week in the second patient, based on his urinary free cortisol (UFC) level. The patients responded to cabergoline treatment with normal UFC levels on the 4th and 6th months of treatment. The boys reached complete remission at the end of the 17th and 24th months, respectively. Cabergoline is effective in the control of cortisol secretion and can be considered as a first-line treatment in cases of CD.

Topics: Adolescent; Cabergoline; Dopamine Agonists; Ergolines; Humans; Hypertension; Male; Petrosal Sinus Sampling; Pituitary ACTH Hypersecretion; Remission Induction

An association between ergot-derived dopamine agonists and asymptomatic valvular heart disease in Parkinson's disease has been established. For safe use of these agonists, it is important to specify those at high risk for valvular heart disease among patients with Parkinson's disease. We performed a nested case-control study of 223 patients with Parkinson's disease. In results of multivariable logistic analyses, use of pergolide, use of cabergoline, age, male sex, and hypertension were independent significant risk factors for left-sided valvular regurgitation. In patients receiving cabergoline or pergolide, elderly (>or=70 years) hypertensive patients had a markedly high risk for valvular regurgitation (odds ratio 94.5) as compared to non-elderly (<70 years) patients without hypertension. The risk of valvular regurgitation caused by pergolide or cabergoline was found to be highly enhanced by comorbid hypertension or aging, suggesting that special attention should be paid when prescribing cabergoline or pergolide for those patients.

Topics: Age Factors; Aged; Benzothiazoles; Bromocriptine; Cabergoline; Case-Control Studies; Dopamine Agonists; Echocardiography; Ergolines; Female; Heart Valve Diseases; Humans; Hypertension; Male; Parkinson Disease; Pergolide; Pramipexole; Risk Factors

Topics: Aged; Analgesics, Opioid; Anesthesia, General; Cabergoline; Dopamine Agonists; Dopamine Uptake Inhibitors; Drug Interactions; Ergolines; Female; Humans; Hypertension; Restless Legs Syndrome; Selective Serotonin Reuptake Inhibitors; Spinal Fusion; Tramadol

Grooming behaviour induced by exposure to a novel environment was studied in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). The dopamine D1 receptor antagonist, SCH 23390, and the dopamine D2 receptor agonist, quinpirole, were used to study brain dopamine systems in these rat strains, via their effects on grooming behaviour. The total grooming behaviour displayed in a 50-min observation period was significantly lower in SHR than in WKY. Except for the paw licking component no differences between the two strains were observed in the separate behavioural elements of grooming behaviour. SCH 23390 and quinpirole were found to suppress novelty-induced grooming behaviour of both strains. In SHR, grooming behaviour was less suppressed by SCH 23390, whereas the suppression by quinpirole was more pronounced than in WKY. These results indicate that there are alterations in central dopamine systems in SHR, probably involving changes both in dopamine D1 and D2 receptor mechanisms in the brain.

Topics: Animals; Benzazepines; Dopamine; Ergolines; Grooming; Hypertension; Male; Motor Activity; Quinpirole; Rats; Rats, Inbred SHR; Rats, Inbred WKY

Using an in vivo microdialysis method, we found that the extracellular concentrations of dopamine and its main metabolite dihydroxyphenylacetic acid (DOPAC) were lower in the caudate nucleus of 8-week-old spontaneously hypertensive rats (SHR) than in the same area of age-matched normotensive Wistar-Kyoto rats (WKY). No differences in the extracellular concentrations of dopamine and DOPAC were found between renal and deoxycorticosterone acetate (DOCA)-salt hypertensive rats when compared to their respective controls. After subcutaneous administration of the dopamine D2 receptor agonist quinpirole (10, 33 and 100 micrograms/kg), the amount of dopamine and DOPAC in the dialysates was diminished dose dependently. The quinpirole-mediated inhibition of dopamine release was more pronounced in SHR than in WKY, whereas inhibition of the extracellular DOPAC concentration was not different. Compared to WKY, the dose-response curve for the inhibition of dopamine release by quinpirole was shifted to the left in SHR and the maximal inhibition in response to the highest dose was significantly greater. Renal and DOCA-salt hypertensive rats showed no differences in the quinpirole-induced inhibition of the extracellular concentrations of striatal dopamine and DOPAC compared to their controls. The present findings on changes in dopaminergic neurotransmission and D2 autoreceptor-mediated modulation of dopamine release in genetically hypertensive rats but not in rats with experimentally induced hypertension provide further evidence for the hypothesis that alterations in the nigrostriatal dopamine system may be involved in the initiation of the development of spontaneous hypertension.

Topics: 3,4-Dihydroxyphenylacetic Acid; Animals; Blood Pressure; Caudate Nucleus; Desoxycorticosterone; Dialysis; Dopamine; Dopamine Agents; Dose-Response Relationship, Drug; Ergolines; Heart Rate; Hypertension; Male; Quinpirole; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Rats, Inbred WKY; Receptors, Dopamine; Receptors, Dopamine D2; Synaptic Transmission

Intracerebroventricular administration of serotonin (5-HT) to conscious rats increases mean arterial pressure (MAP) and decreases heart rate. To determine the mechanisms involved, 5-HT (2.5 micrograms) was injected intracerebroventricularly into conscious rats pretreated with various neurotransmitter and hormone antagonists. The selective 5-HT2 antagonist LY 53857 abolished the increase in MAP and the bradycardia elicited by 5-HT. The increase in MAP produced by 5-HT was potentiated by chlorisondamine (a ganglionic antagonist), unaffected by prazosin (an alpha 1-antagonist) or a vasopressin V1 antagonist alone, but eliminated by the combined pretreatment with prazosin plus the vasopressin antagonist. In contrast, the bradycardia was eliminated by either the vasopressin V1 antagonist or chlorisondamine. In conclusion, 5-HT injected into the lateral cerebral ventricle of conscious rats induces sympathoexcitation and the release of vasopressin, which results in an increase in MAP; 5-HT also elicits a bradycardia mediated through an interaction of the autonomic nervous system with circulating vasopressin.

Topics: Animals; Autonomic Nervous System; Blood Pressure; Bradycardia; Chlorisondamine; Ergolines; Heart Rate; Hypertension; Injections, Intraventricular; Male; Prazosin; Rats; Rats, Inbred Strains; Serotonin; Serotonin Antagonists; Vasopressins

The mode of action of i.v. injected ketanserin, LY 53857 and other 5-hydroxytryptamine (5-HT2) receptor antagonists in lowering blood pressure was examined in anesthetized and pithed spontaneously hypertensive rats (SHR). In pithed SHR, LY 53857 (1 mg kg-1) had no effect on alpha-1 or alpha-2 adrenoceptors, but ketanserin (1 mg kg-1) had some potency as an alpha-1 adrenoceptor antagonist, being approximately 100 times less potent than prazosin. Both ketanserin and LY 53857 (0.01 mg kg-1) markedly antagonized the pressor response to 5-HT. In pentobarbitone-anesthetized SHR, ketanserin and LY 53857 (1 mg kg-1) were equieffective at lowering diastolic blood pressure (DBP) subsequent to prazosin (1 mg kg-1), although ketanserin (1 mg kg-1) was more effective at lowering DBP in the absence of prazosin. The blood pressure lowering effects of LY 53857 were unaffected by the peripherally acting 5-HT2 receptor antagonist BW 501C. Neither LY 53857 nor ketanserin lowered DBP in pithed rats. It is concluded that ketanserin in high doses lowers DBP in anesthetized SHR partly by alpha-1 adrenoceptor blockade, but that ketanserin and LY 53857 in high doses have additional blood pressure lowering properties, unrelated to peripheral 5-HT2 receptor blockade.

Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Anesthesia; Animals; Blood Pressure; Ergolines; Heart Rate; Hypertension; Ketanserin; Male; Prazosin; Rats; Rats, Inbred SHR; Receptors, Adrenergic, alpha; Receptors, Serotonin; Serotonin Antagonists; Tetrahydronaphthalenes; Xylazine

Topics: Animals; Anti-Anxiety Agents; Anxiety; Disease Models, Animal; Ergolines; Hypertension; Nicergoline; Norepinephrine; Rats; Rats, Inbred Strains; Scopolamine

Our previous studies have demonstrated: 1) that i.v. quinpirole (LY171555), a selective dopamine D2 receptor agonist, has a dose-dependent pressor effect in conscious rats which is mediated by activation of sympathetic outflow and vasopressinergic activity, and 2) that the activity of central dopaminergic neurons is reduced in deoxycorticosterone acetate (DOCA)/NaCl hypertensive rats. To elucidate the role of central and peripheral dopaminergic systems in the pathogenesis of DOCA/NaCl hypertension, we examined the effects of quinpirole on mean arterial pressure, heart rate, plasma norepinephrine, epinephrine, arginine vasopressin and atrial natriuretic peptide (ANP) in conscious 4-week-old DOCA/NaCl hypertensive and normotensive control rats. Quinpirole (1 mg/kg i.v.) increased mean arterial pressure in both groups, but the pressor response was attenuated in DOCA/NaCl rats. Paradoxically, quinpirole-induced increments in plasma norepinephrine, epinephrine and arginine vasopressin were greater in DOCA/NaCl rats. In addition, quinpirole induced a 2-fold increase in plasma ANP (P less than .01) in both DOCA/NaCl and control rats. Pretreatment with domperidone (2.5 mg/kg i.v.), a peripherally acting dopamine D2 antagonist, enhanced the maximum pressor response to quinpirole in both groups, restored the quinpirole-induced pressor response to control levels in the DOCA/NaCl rats and blocked the stimulatory effect of quinpirole on ANP release in both groups. These data indicate that peripheral dopamine D2 receptors modulate ANP secretion in the rat. The observation that the quinpirole-induced increment in plasma ANP was enhanced in DOCA/NaCl rats supports the hypothesis that the blunted pressor response to quinpirole in this model is related to enhanced ANP release.

Topics: Animals; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Desoxycorticosterone; Domperidone; Dopamine; Epinephrine; Ergolines; Hemodynamics; Hypertension; Male; Norepinephrine; Quinpirole; Radioimmunoassay; Rats; Rats, Inbred Strains; Receptors, Dopamine

Topics: Animals; Blood Pressure; Dose-Response Relationship, Drug; Ergolines; Hypertension; In Vitro Techniques; Male; Rabbits; Rats; Rats, Inbred SHR; Receptors, Serotonin; Serotonin Antagonists; Uracil

Our previous studies have demonstrated that the specific dopamine D2 receptor agonist, quinpirole (LY171555), has a pressor effect in conscious normotensive rats and that this is accompanied by a centrally mediated increase in sympathetic activity and arginine vasopressin release. This pressor response to quinpirole is blunted in the DOCA/NaCl hypertensive rat. To examine the hypothesis that the responsiveness of the central noradrenergic and serotonergic systems to quinpirole treatment is altered in DOCA/NaCl rats, the norepinephrine (NE), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) contents of hypothalamic and brainstem areas were measured in 4-week DOCA/NaCl hypertensive and H2O control rats 15 minutes after the intravenous administration of quinpirole (1 mg/kg). The results demonstrate that quinpirole selectively reduced (26%) posterior hypothalamic NE content in control rats, but not in DOCA/NaCl hypertensive rats. The NE content in the spinal cord and 5-HIAA content in the pons were greater in DOCA/NaCl rats than in normotensive controls in both saline and quinpirole treated groups. Our data suggest that the specific D2 agonist may effect its central pressor response by stimulating NE release from posterior hypothalamic area, a "pressor" region of hypothalamus, and that this D2 agonist induced pressor mechanism may be blunted in DOCA/NaCl hypertension.

Topics: Animals; Brain; Desoxycorticosterone; Ergolines; Hydroxyindoleacetic Acid; Hypertension; Hypothalamus; Male; Norepinephrine; Quinpirole; Rats; Rats, Inbred Strains; Saline Solution, Hypertonic; Serotonin; Spinal Cord

Our previous studies have demonstrated that LY171555 (quinpirole), a specific dopamine (DA) D2-receptor agonist, has a pressor effect in the conscious rat which is accompanied by increased sympathetic outflow and arginine vasopressin release. To test the hypothesis that LY171555 inhibits in vivo release of DA and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), from central dopaminergic neurons of the conscious, freely moving rat by activation of presynaptic DA receptors in the central nervous system and that this mechanism may be altered in the desoxycorticosterone acetate (DOCA)/NaCl model of hypertension, we used the in vivo push-pull perfusion method to study the effect of LY171555 on central DA release in normotensive and DOCA/NaCl-hypertensive rats. Levels of the DOPAC and HVA were measured in striatal perfusates by HPLC before and after administration of LY171555 (1 mg/kg, i.v.) of conscious, unrestrained 4-week DOCA/NaCl hypertensive and uninephrectomized H2O control rats. There were no significant differences in basal striatal HVA (80 +/- 12 vs 89 +/- 11 pg/min; DOCA/NaCl vs control) or DOPAC levels (37 +/- 5 vs 49 +/- 17 pg/min; DOCA/NaCl vs control) during the entire 240-min collection period. LY171555 significantly reduced HVA and DOPAC levels in perfused striatum in both normotensive control and DOCA/NaCl-hypertensive rats. The LY171555-induced suppression in HVA levels was significantly greater in DOCA/NaCl rats (delta = 60.7 +/- 3.6%) than in H2O controls (delta = 49.0 +/- 3.5%, P less than 0.05). Pretreatment with metoclopramide (10 mg/kg, i.v.), a specific central and peripheral DA D2-receptor antagonist, completely blocked the suppressive effects of LY171555 on HVA and DOPAC levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 3,4-Dihydroxyphenylacetic Acid; Animals; Chromatography; Corpus Striatum; Desoxycorticosterone; Dopamine; Dopamine Antagonists; Ergolines; Homovanillic Acid; Hypertension; Male; Metoclopramide; Quinpirole; Rats; Rats, Inbred Strains; Receptors, Dopamine; Receptors, Dopamine D2; Sodium Chloride

Our previous studies have demonstrated that administration of quinpirole (LY171555), a potent and highly selective dopamine (DA) D2 receptor agonist, to conscious Sprague-Dawley rats produces increases in arterial pressure through the activation of sympathetic outflow and vasopressinergic activity. To test the hypotheses that quinpirole inhibits in vivo release of DA from central dopaminergic neurons by activation of DA receptors in the central nervous system (CNS) and that this mechanism may be altered in the desoxycorticosterone acetate (DOCA)/NaCl model of hypertension, we examined the effects of quinpirole on stores of DA and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in brain regions of 4-week DOCA/NaCl-hypertensive rats and their normotensive controls. Levels of DA and DOPAC were measured in brain regions by HPLC 15 min after the i.v. administration of quinpirole (1 mg/kg). Quinpirole resulted in a significant increase in DA stores and decrease in DOPAC stores in most brain regions examined in both DOCA/NaCl-hypertensive rats and normotensive controls, presumably by inhibiting DA release through a presynaptic mechanism. In the vehicle-treated groups, DA stores in the anterior hypothalamus and DOPAC stores in the nucleus accumbens were lower in DOCA/NaCl-hypertensive rats than in H2O controls. Following quinpirole administration, DA stores in the anterior hypothalamus increased significantly in DOCA/NaCl-treated rats but not in H2O controls and DOPAC stores in the nucleus accumbens decreased significantly in H2O control rats but not in DOCA/NaCl-treated rats. These observations provide further evidence for the presence of inhibitory DA D2 receptors which modulate the activity of dopaminergic neurons in the CNS.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 3,4-Dihydroxyphenylacetic Acid; Animals; Brain Chemistry; Desoxycorticosterone; Dopamine; Ergolines; Hypertension; Male; Phenylacetates; Quinpirole; Rats; Rats, Inbred Strains; Receptors, Dopamine; Receptors, Dopamine D2; Sodium Chloride

Topics: Aged; Aged, 80 and over; Antihypertensive Agents; Drug Therapy, Combination; Ergolines; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Nicergoline; Random Allocation

Topics: Animals; Behavior, Animal; Electroshock; Ergolines; Exploratory Behavior; Female; Hypertension; Male; Metergoline; Motor Activity; Nicergoline; Rats; Rats, Inbred Strains; Stress, Physiological

In pentobarbital-anesthetized normotensive dogs, clonidine (20.0 micrograms/kg i.v.), in contrast to pergolide (30.0 micrograms/kg i.v.), reduced significantly both aortic blood pressure and plasma concentration of norepinephrine. However, in dogs that had been made hypertensive by sectioning the vagi and carotid sinus nerves, pergolide, like clonidine, lowered the blood pressure and plasma concentrations of epinephrine and norepinephrine that were enhanced markedly by deafferentation. Furthermore, in this preparation pergolide decreased the calculated resistance in vascular regions supplied by the upper abdominal aorta and the innervated femoral and renal arteries, but it increased vascular resistance in the denervated hind leg. Pergolide (1.0 microgram/kg) injected intracisternally (i.c.m.) induced a fall in blood pressure of comparable magnitude to that produced by a 30 times higher i.v. dose. Intravenously and i.c.m. administered pergolide lowered blood pressure by acting at distinct anatomical sites inasmuch as i.v. sulpiride blocked the effects of i.v. but not i.c.m. pergolide. The combination of sulpiride plus yohimbine injected i.c.m. was necessary to abolish the decrease in blood pressure evoked by i.c.m. pergolide. In atropinized spinal dogs, i.v. pergolide inhibited the vasoconstriction elicited by electrical stimulation of the lumbar sympathetic chain, an effect which was antagonized by sulpiride. Similarly, pergolide (30.0 micrograms/kg i.v.) like clonidine, reduced the heart rate and coronary venous plasma norepinephrine concentration raised by sustained electrical stimulation of the cardioaccelerator nerve. Sulpiride, but not phentolamine, antagonized this pergolide-induced inhibition of sympathetic nerve function. In chlorisondamine-pretreated dogs, pergolide produced a transient pressor response due to stimulation of postsynaptic vascular alpha-2 adrenoceptors. In conclusion, the failure of i.v. pergolide to decrease aortic blood pressure in pentobarbital-anesthetized normotensive dogs is presumably due to the inability of pergolide to produce a significant inhibition of the vascular sympathetic tone in this preparation. However, in neurogenic hypertensive dogs which are characterized by an elevated level of sympathetic drive, i.v. pergolide reduced blood pressure and aortic plasma norepinephrine concentration. These effects of pergolide are compatible with a DA-2 dopamine receptor stimulation on peripheral sympathetic nerve fibers. In co

Topics: Anesthesia; Animals; Blood Pressure; Clonidine; Denervation; Dogs; Electric Stimulation; Ergolines; Female; Heart; Heart Rate; Hemodynamics; Hypertension; Male; Norepinephrine; Pergolide; Receptors, Dopamine; Receptors, Dopamine D2; Sulpiride; Vagotomy; Vascular Resistance; Vasoconstriction

Spontaneously hypertensive rats (SHR) exhibit a significantly higher level of spontaneous locomotor activity than age-matched normotensive controls (WKY). The direct-acting dopamine agonists, apomorphine and pergolide, produced a biphasic effect on locomotor activity levels in normotensive controls. Low doses of these agonists decreased activity levels, while higher doses of these agonists dramatically stimulated activity. In marked contrast to these results was the effect observed in the SHR, in which these agonists at all doses tested decreased activity. Amphetamine, a dopamine releaser, stimulated activity levels in both the WKY and SHR; however, the magnitude of the increase was somewhat attenuated in the SHR.

Topics: Amphetamine; Animals; Dopamine; Dose-Response Relationship, Drug; Ergolines; Hypertension; Motor Activity; Pergolide; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, Dopamine

In order to test the therapeutic action of nicergoline during peroperative arterial hypertension, an intravenous perfusion of 5 mcg/kg/mn average dose was given to 15 patients which presented a peroperative increase of Systolic Blood Pressure (SBP) greater than 30% when compared with preanaesthetic corresponding value. The haemodynamic evolution was monitored, using non invasive method (except for central venous pressure, CVP). Particularly Aortic Blood Flow (ASF) was measured by ultrasonic means using specially designed intraoesophageal probe and flow meter including A-Scan and Doppler Velocity meter. SBP increased in 43% during hypertensive peak (initial level mean 129, +/- 12.6 mmHg; hypertensive peak, mean 185 +/- 16.80 mmHg; p less than 0.001). Ten minutes after the beginning of nicergoline perfusion, SBP showed a significative decrease (mean 141.4 +/- 11.20 mmHg, +9%). At the end of operation the SBP was nearly to average initial value (mean 135, +/- 11.85 mmHg; +4.5%). Diastolic Blood Pressure and Mean Blood Pressure presented similar variations. ABF decreased significatively during hypertensive peak (Initial ABF value means 3.49, +/- 0.99 l/mn, hypertensive peak ABF value means 2.68, +/- 0.54 l/mn, -25%, p less than 0.01). Nicergoline perfusion induced a partial recovery of ABF (mean 3.23 +/- 0.56 l/mn, +8%, p less than 0.05). This one was confirmed at the end of operation (mean 3.6 +/- 0.56 l/mn; -4% N.S.). Heart rate did not change significantly during monitoring period. From this results is seems that nicergoline perfusion induces a protection of hypertensive patients during peroperative decompensation.

Topics: Adult; Aged; Anesthesia, General; Aorta; Blood Pressure; Central Venous Pressure; Ergolines; Female; Heart Rate; Humans; Hypertension; Intraoperative Complications; Male; Middle Aged; Monitoring, Physiologic; Nicergoline; Vascular Resistance

In conscious spontaneously hypertensive rats, pergolide (50.0 micrograms/kg s.c.) produced a sustained decrease in tail artery pressure which was blocked by haloperidol (1.0 mg/kg s.c.) pretreatment. In anesthetized spontaneously hypertensive rats this effect was accompanied by a fall in total peripheral resistance inasmuch as pergolide did not significantly change cardiac output. In anesthetized normotensive rats, pergolide (30.0 micrograms/kg i.v.) also lowered blood pressure. This effect was not significantly modified by adrenalectomy, methysergide, idazoxan (alpha-2 adrenoceptor antagonist), vagotomy alone or plus ligation of carotid arteries or plus atenolol, but was entirely prevented by domperidone or sulpiride pretreatment and was reverted to a pressor response (due to stimulation of alpha adrenoceptors and 5-hydroxytryptamine receptors) by blockade of ganglionic transmission with chlorisondamine. Pergolide given either i.v. or into the cisterna magna or the lateral cerebral ventricle produced changes in blood pressure of the same magnitude. In intact or adrenalectomized rats, i.v. pergolide significantly lowered plasma norepinephrine concentration. Furthermore, in saline but not sulpiride-pretreated pithed rats, pergolide reduced the pressor responses and the accompanying increases in plasma norepinephrine evoked by electrical stimulation of the spinal cord. However, pergolide failed to modify the vascular reactivity to several pressor agents and lacked beta-2 and DA-1 dopamine receptor agonist properties. These results indicate that the decrease in blood pressure produced by pergolide can be accounted for by an inhibition of sympathetic tone resulting from stimulation of peripheral neuronal dopamine receptors. A possible central contribution remains to be substantiated. The pronounced bradycardia produced by pergolide (30.0 micrograms/kg i.v.) in anesthetized intact rats was partly reduced by vagotomy, methylatropine, domperidone, sulpiride, idazoxan, phentolamine or atenolol. The effects of pergolide in vagotomized rats were further diminished by domperidone but they were blocked by the combination of phentolamine or idazoxan plus domperidone. In rats pretreated with atenolol or in rats with the cervical section of spinal cord and the low level of heart rate increased with an isoprenaline infusion, the decrease in heart rate produced by pergolide was abolished by domperidone, methylatropine or idazoxan. In pithed rats, pergolide changed neither

Topics: Adrenalectomy; Animals; Antiparkinson Agents; Autonomic Nervous System; Blood Pressure; Clonidine; Decerebrate State; Dose-Response Relationship, Drug; Ergolines; Heart Rate; Hypertension; Male; Methysergide; Norepinephrine; Pergolide; Phenoxybenzamine; Rats; Rats, Inbred Strains; Receptors, Dopamine; Spinal Cord; Vascular Resistance; Vasopressins

LY141865, a dopamine agonist selective for D2 dopamine receptors, caused hypomotility at low doses (0.01 and 0.1 mg/kg) and hypermotility at high doses (1 and 10 mg/kg) after i.p. injection into normotensive rats (WKY). In age-matched hypertensive rats (SHR), LY141865 caused hypomotility (not hypermotility) at all of these doses. The basal locomotor activity was higher in SHR than in WKY, but striatal concentrations of dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, and of serotonin and its metabolite, 5-hydroxyindoleacetic acid, were not different between the two groups of rats. The specific binding of a dopamine receptor radioligand, tritiated pergolide, in striatum and mesolimbic regions, did not differ in SHR compared with WKY. In contrast to the lack of locomotor stimulation in SHR, other dopaminergic responses to LY141865 occurred in SHR as well as WKY. For instance, LY141865 decreased striatal and mesolimbic concentrations of 3,4-dihydroxyphenylacetic acid and homovanillic acid, increased striatal and mesolimbic concentrations of acetylcholine, decreased hypothalamic concentrations of epinephrine, increased serum corticosterone concentration and decreased serum prolactin concentration in SHR as in WKY. Because radioligand-labeled dopamine receptors and several LY141865 responses mediated by dopamine receptors did not differ appreciably in SHR compared with WKY, the lack of behavioral hypermotility in response to LY141865 in SHR may be due to abnormalities in some synaptic mechanisms beyond dopamine receptor activation that are involved in the expression of increased locomotion in response to the dopamine agonist.

Topics: Animals; Behavior, Animal; Corpus Striatum; Corticosterone; Dopamine; Ergolines; Hypertension; Motor Activity; Neurotransmitter Agents; Prolactin; Quinpirole; Rats; Rats, Inbred Strains; Receptors, Dopamine

Cardiovascular effects of the dopamine receptor agonists, bromocriptine and lergotrile, were examined in renal hypertensive rats (RHR), spontaneously hypertensive rats (SHR) and in normotensive rats (NTR). In SHR, bromocriptine at 0.3 and 1.0 mg/kg i.p. and lergotrile at 0.3 mg/kg i.p. produced significant decreases in blood pressure and heart rate and the effects were prevented by haloperidol pretreatment. These results are consistent with the hypothesis that bromocriptine- and lergotrile-induced cardiovascular effects are due to a reduction in sympathetic tone via activation of neuronal dopamine receptors. In contrast to SHR, bromocriptine as well as lergotrile, at doses of 0.3 mg/kg i.p., were ineffective in RHR. Only at the 1 mg/kg i.p. dose, both the agents reduced blood pressure in RHR, but increased heart rate and only the effects of bromocriptine were antagonized by haloperidol. The magnitude and the duration of the hypotensive effect produced by both the agents were smaller in RHR than in SHR. The ganglion blocking agent, chlorisondamine, reduced blood pressure equally in RHR and SHR, but not in NTR, indicating a role for the sympathetic nervous system in the maintenance of high blood pressure in both SHR and RHR. It is further suggested that neuronal dopamine receptors that mediate reduction in resting sympathetic tone are less sensitive in RHR as compared to SHR.

Topics: Animals; Blood Pressure; Bromocriptine; Ergolines; Heart Rate; Hypertension; Hypertension, Renal; Male; Rats; Rats, Inbred Strains

Topics: Adrenal Gland Neoplasms; Ergolines; Female; Humans; Hypertension; Injections, Intravenous; Middle Aged; Nicergoline; Pheochromocytoma; Postoperative Complications

LY53857 was a potent antagonist of vascular contraction to serotonin, which is mediated by serotonergic (5-HT2) receptors, with a dissociation constant in vitro of 5.4 X 10(-11) M. Unlike several other serotonin antagonists, LY53857 showed minimal affinity for vascular alpha adrenergic receptors (dissociation constant of 1.4 X 10(-5) M). Thus, LY53857 was a highly potent and selective antagonist at 5-HT2 receptors. In vivo activity paralleled the in vitro observations. In pithed spontaneously hypertensive rats (SHR), LY53857 at 0.1 and 3.0 mg/kg i.p. produced a 22-and 480-fold shift, respectively, in the pressor response to serotonin whereas LY53857 at 10 mg/kg did not alter the pressor response to the alpha receptor agonist, methoxamine. Furthermore, LY53857 administered peripherally also inhibited central serotonin receptors, as evidenced by blockade of the serum corticosterone increase produced by the central actions of the serotonin agonist, quipazine, and by antagonism of tryptamine-induced convulsions in rats. LY53857 in doses that blocked the pressor response to serotonin and that blocked central serotonin receptors did not lower mean arterial blood pressure in the SHR. Thus, the lack of effectiveness of LY53857 to lower blood pressure in the SHR indicates that blockade of both central and vascular serotonin receptors is not a sufficient mechanism to lower blood pressure in this model of hypertension.

Topics: Animals; Blood Pressure; Ergolines; Heart Rate; Hypertension; Male; Muscle, Smooth, Vascular; Pressoreceptors; Rats; Rats, Inbred Strains; Receptors, Adrenergic, alpha; Receptors, Serotonin; Serotonin Antagonists

Six consanguine monogamous SHR couples (G 1) were treated from 5 weeks of age on with an alpha blocker, nicergoline, 100 mcg. kg-1 day-1 i.p. Male rats were treated without interruption; treatment was withheld in female rats from delivery to weaning. They were compared with six similar SHR couples who were only daily i.p. injected with the same volume of solvent in the same conditions, as controls. Second (G 2) and third (G 3) generation rats (untreated) were studied. In G 1 rats, systolic blood pressure (SBP) was decreased, and no change was found in heart rate (H R), heart weight to body weight ratio (HW/BW), hypothalamic and bulbar noradrenaline content (HNA,BNA). In G 2 rats, SBP, BNA and plasma renin activity were significantly decreased, all other parameters being unchanged. No parameter change was observed in G 3 rats. We think that such long acting effects after antenatal treatment could only be due to an action on the origin of the SHR hypertension.

Topics: Animals; Blood Pressure; Ergolines; Female; Heart Rate; Hypertension; Male; Myocardium; Nicergoline; Norepinephrine; Rats; Renin

Topics: Animals; Blood Pressure; Brain Ischemia; Cats; Cerebrovascular Circulation; Electroencephalography; Ergolines; Homeostasis; Hypertension; Hypotension; Nifedipine; Papaverine; Vasodilation

Topics: Adrenal Gland Neoplasms; Ergolines; Female; Humans; Hypertension; Intraoperative Care; Middle Aged; Nicergoline; Pheochromocytoma

The cardiovascular actions of the dopaminergic ergoline, pergolide were examined in pentobarbital-anesthetized dogs. When administered intravenously (i.v.) to dogs made hypertensive by sino-aortic deafferentation, pergolide produced a sustained reduction in blood pressure, dilatation of the hindlimb vasculature and bradycardia. The antihypertensive action of pergolide in neurogenic hypertensive dogs was converted into a pressor action when it was given to dogs pretreated with i.v. sulpiride or hexamethonium plus atropine. Pergolide caused significant impairment of renal vasoconstriction elicited during stimulation of renal sympathetic nerves but not that caused by exogenous norepinephrine. The inhibitory action of pergolide on renal sympathetic nerve function was antagonized by sulpiride suggesting that pergolide activated presynaptic dopamine receptors. Direct administration of pergolide within the central nervous system via the cisterna magna (i.c.) to normotensive dogs also resulted in hypotension, bradycardia and iliac vasodilatation. The central actions of pergolide were prevented by sulpiride (i.c.) but not by yohimbine (i.c.), which indicates that specific activation of central dopamine receptors was responsible for these actions of pergolide. The antihypertensive, bradycardic and iliac vasodilatory actions of i.v. pergolide in neurogenic hypertensive dogs were significantly attenuated by i.c. sulpiride. It was determined that while this dose of sulpiride antagonized central dopamine receptors, it did not antagonize peripheral presynaptic dopamine receptors. These results suggest that pergolide exerts antihypertensive and bradycardic actions via simultaneous stimulation of dopamine receptors in the brain and on postganglionic sympathetic neurons. While presynaptic dopamine receptor activation contributes to the blood pressure lowering action of pergolide, stimulation of central dopamine receptors appears to be the dominant mechanism by which pergolide elicits the observed antihypertensive and bradycardic effects. Pergolide appears to lower blood pressure by a novel mechanism of action and may offer an additional therapeutic approach for the treatment of hypertension.

Topics: Animals; Blood Pressure; Cardiovascular Agents; Cardiovascular System; Central Nervous System; Dogs; Ergolines; Female; Heart Rate; Hypertension; Male; Norepinephrine; Pergolide; Peripheral Nerves; Receptors, Dopamine; Renal Circulation; Sulpiride; Vascular Resistance

The effects on blood pressure and heart rate of a new ergoline derivative, 2(R,S)-Cyano-3-(6-methylergolin-8 beta-yl)-propionamide (355/1057), were evaluated in different models of experimental hypertension as well as in normotensive rats, dogs and cats. Its interference with sympathetic neurotransmission was also studied in anaesthetized cats and dogs and in pithed rats. Dose-related hypotensive effects were found after single oral, intraduodenal and intravenous administration. In all the studied experimental models 355/1057 showed a prompt onset of action and a prolonged effect on blood pressure at low doses without substantially modifying heart rate. Some comparative results obtained with other commercially available antihypertensive agents are also reported. One month daily oral administration in SH-rats produced an antihypertensive effect persisting trough the entire experiment with no signs of tachyphylaxis. In anaesthetized dogs 355/1057 inhibited sthe pressor response elicited by bilateral carotid occlusion and in anaesthetized cats it reduced the response of the nictitating membrane elicited by electrical stimulation of both the pre- and post-ganglionic fibers but not by norepinephrine bolus injection.

Topics: Anesthesia; Animals; Antihypertensive Agents; Blood Pressure; Cats; Dogs; Ergolines; Heart Rate; Hemodynamics; Hypertension; Hypertension, Renal; Male; Rats; Rats, Inbred Strains; Species Specificity

Topics: Anesthesia; Animals; Antihypertensive Agents; Dogs; Ergolines; Heart Rate; Hypertension; Male; Quinpirole; Rats; Rats, Inbred Strains; Receptors, Dopamine; Sympathetic Nervous System; Vasoconstriction

Six consanguine monogamous SHR couples (G1) were treated from 5 weeks of age on with an alpha blocker, nicergoline, 0.1 mg/kg/day i.p.. Male rats were treated without interruption; treatment was withheld in female rats from delivery to weaning. They were compare to six similar SHR couples who were only daily i.p. injected with the same volume of solvent in the same conditions as controls, as well as with naive (untreated) rats. Second (G2) and third (G3) generation rats (untreated) were studied. In G1 rats, systolic blood pressure (SBP), heart rate, heart weight/body weight ratio and bulbar noradrenaline content were decreased (compared to control or naive rats), while plasma renin activity (PRA) and hypothalamic noradrenaline content were not changed. In G2 rats, SBP and PRA were decreased, all other parameters being unchanged. No parameter was changed in G3 rats. This appears to be the first report of a preventive effect of antenatal treatment on the development of hypertension in SHR.

Topics: Animals; Blood Pressure; Body Weight; Ergolines; Female; Heart Rate; Hypertension; Hypothalamus; Male; Nicergoline; Norepinephrine; Rats; Rats, Inbred Strains

Topics: Animals; Antihypertensive Agents; Dogs; Electric Stimulation; Ergolines; Female; Hemodynamics; Hypertension; Male; Neurons, Afferent; Pergolide; Receptors, Dopamine; Renal Circulation; Sulpiride

The possible alteration of central dopaminergic (DA) function, which accompanies the development and persistence of hypertension, was studied in SHRSP by measuring the lisuride-induced locomotor activity and the swimming ability. 1) When administered at a dosage of 50 micrograms/kg, lisuride, a DA agonist, induced significant increases of the locomotor activity in one- and 2-month-old Wistar Kyoto rats (WKY), but not in the 6 month-old rat. Differing from the response of WKY, SHRSP showed only a moderate increase in the locomotor activity at the age of one month (means of systolic blood pressure: 128 mmHg) and apparently no increase at the age of 2 months (176 mmHg). In 6 month-old SHRSP (238 mmHg), hypomotility but not hypermotility was induced by the lisuride administration. 2) Though no significant difference was detected at the age of 4 months, the swimming ability of SHRSP at the age of 8 months was deteriorated significantly as compared to that of WKY, and the impaired swimming performance of SHRSP was improved by the administration of lisuride. These results indicate that some alterations in the synaptic sites of the central DA neuron occurred already at an early stage of the hypertensive development, followed under persistent hypertension by the progressive deterioration of the motor-coordination ability as detected in the swimming ability.

Topics: Age Factors; Animals; Cerebrovascular Disorders; Ergolines; Hypertension; Lisuride; Locomotion; Male; Rats; Rats, Inbred Strains; Receptors, Dopamine; Swimming

Eight month-old SHRSP were treated s.c. with lisuride (50 micrograms/kg per day) for 5 weeks to examine the effect of the central dopaminergic agonist on the deterioration of swimming ability that occurred and progressed under persistent hypertension. General observations on signs and symptoms and histopathological examinations were also carried out with the same rats to evaluate the drug effect on the deterioration of hypertensive symptoms. The poor swimming performance of hypertensive SHRSP was improved significantly by the direct action of lisuride with a maximal effect at the 2nd week of the treatment, although the progress of the deterioration itself was not prevented by the chronic treatment. One week after the drug treatment, 2 out of 8 rats in the control group but none in the lisuride-treated group exhibited the abnormal behavior with aggressiveness, a typical sign of the occurrence of cerebrovascular lesions. Furthermore, macroscopic and histopathological examinations carried out 2 weeks after the drug treatment revealed that severities of the histopathological lesions such as myocardiac necrosis and arteriolosclerosis in the kidney, adrenal and testis were significantly lower in the lisuride-treated group than in the control.

Topics: Adrenal Glands; Animals; Behavior, Animal; Cerebrovascular Disorders; Ergolines; Hypertension; Kidney; Lisuride; Male; Myocardium; Rats; Rats, Inbred Strains; Swimming

Topics: Animals; Electric Stimulation; Ergolines; Haloperidol; Hemodynamics; Hypertension; Male; Norepinephrine; Rats; Receptors, Adrenergic, alpha; Sympathetic Nervous System; Synaptic Transmission

Topics: Animals; Blood Pressure; Dose-Response Relationship, Drug; Drug Interactions; Ergolines; Hemodynamics; Hypertension; Male; Pergolide; Peripheral Nerves; Rats; Rats, Inbred Strains; Spinal Cord; Sympathetic Nervous System; Synaptic Transmission

Topics: Aged; Arteries; Cerebrovascular Disorders; Ergolines; Female; Humans; Hypertension; Leg; Male; Middle Aged; Myocardial Infarction; Nicergoline; Vascular Diseases

Topics: Aged; Ergolines; Female; Humans; Hypertension; Male; Middle Aged; Myocardial Infarction; Nicergoline

Topics: Ergolines; Hemodynamics; Humans; Hypertension; Injections, Intravenous; Nicergoline

The antihypertensive activity of nicergoline (Sermion), an adrenolytic and vasodilator drug, was tested in rats when hypertensive vascular disease was induced by administration of methylandrostenediol (MAD). Nicergoline not only counteracted the effect of MAD on the systolic blood pressure of the rats, but it also prevented the appearance of vascular lesions usually induced by this type of experimental hypertension on arterioles of several organs such as heart, kidney and brain and of the pancreatic mesenteric region. When given alone, the drug was well tolerated. Since the drug did not interfere with the modification induced by MAD on the adrenal steroidogenesis, as seen by EM studies of the zona fasciculata of the androgen-treated animals, it is likely that it may have exerted its adrenolytic effect on the peripheral vessels of the MAD-induced hypertensive rats.

Topics: Adrenal Glands; Androstenediols; Animals; Blood Pressure; Cytochrome P-450 Enzyme System; Ergolines; Female; Hypertension; Methandriol; Nicergoline; Organ Size; Potassium; Rats; Sodium

Topics: Animals; Antihypertensive Agents; Blood Pressure; Ergolines; Heart Rate; Hypertension; Male; Rats

The acute administration of lergotrile mesylate to normal or spontaneously-hypertensive rats (SHR) causes a prompt reduction in blood pressure. In SHR, doses as small as 0.05 mg kg-1 are effective; maximal reductions in blood pressure are obtained at a dose of 0.25 mg kg-1. Lergotrile may be administered intraperitoneally or orally. Its efficacy as an antihypertensive agent in rats does not diminish significantly when administered twice daily for 7 days. Although lergotrile has been reported to be a dopamine agonist, the present data do not establish the mechanism by which the drug lowers blood pressure.

Topics: Animals; Blood Pressure; Depression, Chemical; Dose-Response Relationship, Drug; Ergolines; Hypertension; Injections, Intraperitoneal; Male; Rats; Time Factors

Plasma-prolactin concentration was up to four times higher in male patients with essential hypertension than in normotensive controls. Oral administration of bromocriptine, a dopaminergic agonist, suppressed plasma-prolactin and lowered arterial pressure. It is proposed that in the hypertensive patients the raised prolactin levels reflect a defect in central dopamine control which is normalised by bromocriptine. The antihypertensive effect of bromocriptine suggests that the dopaminergic system is involved in blood-pressure regulation and that reduced central dopaminergic activity may be a factor in the maintenance of essential hypertension.

Topics: Adult; Antihypertensive Agents; Blood Pressure; Bromocriptine; Dopamine; Ergolines; Humans; Hypertension; Male; Prolactin; Sodium

Topics: Acromegaly; Adult; Blood Pressure; Bromocriptine; Drug Therapy, Combination; Ergolines; Humans; Hydralazine; Hypertension; Male; Propranolol

Topics: Adult; Aged; Arteriosclerosis; Blood Pressure; Cerebrovascular Disorders; Ergolines; Evaluation Studies as Topic; Female; Glomerulonephritis; Heart Block; Humans; Hypertension; Intracranial Arteriosclerosis; Intracranial Embolism and Thrombosis; Male; Memory Disorders; Middle Aged; Vascular Diseases; Vascular Headaches; Vision Disorders

Topics: Antihypertensive Agents; Cerebrovascular Disorders; Chronic Disease; Ergolines; Female; Humans; Hypertension; Male

Topics: Adult; Aged; Cerebrovascular Disorders; Ergolines; Erythrocytes; Female; Giant Cell Arteritis; Headache; Humans; Hypertension; Male; Meningitis; Metabolic Clearance Rate; Middle Aged; Migraine Disorders; Osteoarthritis; Serotonin Antagonists; Sinusitis; Urea; Vascular Headaches

Topics: Adult; Aged; Blood Pressure; Brain; Cerebrovascular Circulation; Ergolines; Female; Glucose; Hemodynamics; Humans; Hypertension; Intracranial Arteriosclerosis; Male; Middle Aged; Oxygen Consumption

Topics: Analgesics; Cerebrovascular Disorders; Ergolines; Ergotamine; Headache; Humans; Hypertension; Hypnotics and Sedatives; Metabolic Diseases; Methysergide; Migraine Disorders; Psychotherapy; Tranquilizing Agents

Topics: Ergolines; Ergot Alkaloids; Humans; Hypertension; Outpatients

Topics: Alkaloids; Cardiovascular Agents; Ergolines; Ergot Alkaloids; Humans; Hypertension

Topics: Blood Pressure; Dihydroergocornine; Ergolines; Humans; Hypertension