thiourea and Hypertension

Aging has a remarkable effect on cardiovascular homeostasis and it is known as the major non-modifiable risk factor in the development of hypertension. Medications targeting sympathetic nerve system and/or renin-angiotensin-aldosterone system are widely accepted as a powerful therapeutic strategy to improve hypertension, although the control rates remain unsatisfactory especially in the elder patients with hypertension. Purinergic receptors, activated by adenine, uridine nucleotides and nucleotide sugars, play pivotal roles in many biological processes, including platelet aggregation, neurotransmission and hormone release, and regulation of cardiovascular contractility. Since clopidogrel, a selective inhibitor of G protein-coupled purinergic P2Y

Topics: Aging; Angiotensin II; Animals; Antihypertensive Agents; Humans; Hypertension; Isothiocyanates; Molecular Targeted Therapy; Purinergic P2 Receptor Antagonists; Reactive Oxygen Species; Receptor, Angiotensin, Type 1; Receptors, Purinergic P2; Thiourea

Topics: Aniline Compounds; Animals; Calcium Signaling; Cardiovascular Diseases; Humans; Hypertension; Kidney; Myocardial Reperfusion Injury; Phenyl Ethers; Reperfusion Injury; Sodium Chloride, Dietary; Sodium-Calcium Exchanger; Thiourea

Hypertension is the most common chronic disease, and is the leading risk factor for death caused by stroke, myocardial infarction, and end-stage renal failure. The critical importance of excess salt intake in the pathogenesis of hypertension is widely recognized. However, the molecular mechanisms underlying salt-sensitive hypertension remain obscure. Recent studies using selective inhibitors and genetically engineered mice provide compelling evidence that salt-sensitive hypertension is triggered by Ca2+ entry through Na+/Ca2+ exchanger type-1 (NCX1) in vascular smooth muscle. Intriguingly, endogenous Na+ pump inhibitors seem to be necessary for NCX1-mediated hypertension. These findings have enabled us to explain how high salt intake leads to hypertension, and further to describe the potential of vascular NCX1 as a new therapeutic or diagnostic target for salt-sensitive hypertension.

Topics: Aniline Compounds; Animals; Drug Design; Humans; Hypertension; Kidney; Mice; Muscle, Smooth, Vascular; Natriuresis; Phenyl Ethers; Sodium; Sodium Chloride, Dietary; Sodium-Calcium Exchanger; Sodium-Potassium-Exchanging ATPase; Thiourea

Nitric oxide (NO) affects mitochondrial activity through its interactions with complexes. Here, we investigated regulations of complex I (C-I) and complex II (C-II) by neuronal NO synthase (nNOS) in the presence of fatty acid supplementation and the impact on left ventricular (LV) mitochondrial activity from sham and angiotensin II (Ang-II)-induced hypertensive (HTN) rats. Our results showed that nNOS protein was expressed in sham and HTN LV mitochondrial enriched fraction. In sham, oxygen consumption rate (OCR) and intracellular ATP were increased by palmitic acid (PA) or palmitoyl-carnitine (PC). nNOS inhibitor, S-methyl-l-thiocitrulline (SMTC), did not affect OCR or cellular ATP increment by PA or PC. However, SMTC increased OCR with PA + malonate (a C-II inhibitor), but not with PA + rotenone (a C-I inhibitor), indicating that nNOS attenuates C-I with fatty acid supplementation. Indeed, SMTC increased C-I activity but not that of C-II. Conversely, nNOS-derived NO was increased by rotenone + PA in LV myocytes. In HTN, PC increased the activity of C-I but reduced that of C-II, consequently OCR was reduced. SMTC increased both C-I and C-II activities with PC, resulted in OCR enhancement in the mitochondria. Notably, SMTC increased OCR only with rotenone, suggesting that nNOS modulates C-II-mediated OCR in HTN. nNOS-derived NO was partially reduced by malonate + PA. Taken together, nNOS attenuates C-I-mediated mitochondrial OCR in the presence of fatty acid in sham and C-I modulates nNOS activity. In HTN, nNOS attenuates C-I and C-II activities whereas interactions between nNOS and C-II maintain mitochondrial activity.

Topics: Angiotensin II; Animals; Cells, Cultured; Citrulline; Electron Transport Complex I; Electron Transport Complex II; Enzyme Inhibitors; Hypertension; Male; Malonates; Mitochondria, Heart; Myocytes, Cardiac; Nitric Oxide Synthase Type I; Oxygen Consumption; Rats; Rats, Sprague-Dawley; Rotenone; Thiourea

The aims of the present study were to determine the mechanism underlying enhanced neuronal nitric oxide synthase (nNOS) activity in the brain of hypertensive Dahl salt-sensitive (DSS) rats and the consequences of enhanced nNOS activity. Male DSS rats were fed either a regular (0.4% NaCl) or high-salt (8% NaCl) diet, with or without 0.25% nifedipine, for 4 weeks. The effects of nifedipine, which lowers blood pressure peripherally, on central nNOS were determined by measuring nNOS activity, as well as the number of nNOS-positive neurons in the brain stem and diencephalon. The effects of chronic (12 days) infusion of 7 μg (0.5 μL/h, i.c.v.) S-methyl-L-thiocitrulline (SMTC; a stereoselective competitive nNOS inhibitor) on mean arterial pressure were assessed in conscious DSS rats using a radiotelemetry system. In addition, the number of central nNOS-positive neurons was compared between DSS and salt-insensitive Sprague-Dawley rats. Normalization of blood pressure by nifedipine attenuated the increase in nNOS activity in the brain stem of DSS rats. Chronic i.c.v. infusion of SMTC further enhanced hypertension in DSS rats. Feeding of a high-salt diet increased nNOS-positive neurons in the lateral parabrachial nucleus, rostral ventrolateral medulla and nucleus tractus solitarius of DSS compared with Sprague-Dawley rats, whereas nNOS-positive neurons in the paraventricular nucleus remained downregulated in DSS rats. The results of the present study suggest that hypertension, rather than a high-salt diet, increases central nNOS activity in hypertensive DSS rats to buffer high blood pressure. However, this compensatory response may be insufficient to relieve salt-induced hypertension.

Topics: Animals; Arterial Pressure; Brain Stem; Citrulline; Disease Models, Animal; Enzyme Inhibitors; Hypertension; Immunohistochemistry; Male; Neurons; Nitric Oxide Synthase Type I; Rats; Rats, Inbred Dahl; Rats, Sprague-Dawley; Sodium Chloride, Dietary; Telemetry; Thiourea

Subplasmalemmal ion fluxes have global effects on Ca(2+) signaling in vascular smooth muscle. Measuring cytoplasmic and mitochondrial [Ca(2+)]and [Na(+)], we previously showed that mitochondria buffer both subplasmalemmal cytosolic [Ca(2+)] and [Na(+)] in vascular smooth muscle cells. We have now directly measured sarcoplasmic reticulum [Ca(2+)] in aortic smooth muscle cells, revealing that mitochondrial Na(+)/Ca(2+) exchanger inhibition with CGP-37157 impairs sarcoplasmic reticulum Ca(2+) refilling during purinergic stimulation. By overexpressing hFis1 to remove mitochondria from the subplasmalemmal space, we show that the rate and extent of sarcoplasmic reticulum refilling is augmented by a subpopulation of peripheral mitochondria. In ATP-stimulated cells, hFis-1-mediated relocalization of mitochondria impaired the sarcoplasmic reticulum refilling process and reduced mitochondrial [Ca(2+)] elevations, despite increased cytosolic [Ca(2+)] elevations. Reversal of plasmalemmal Na(+)/Ca(2+) exchange was the primary Ca(2+) entry mechanism following ATP stimulation, based on the effects of KB-R7943. We propose that subplasmalemmal mitochondria ensure efficient sarcoplasmic reticulum refilling by cooperating with the plasmalemmal Na(+)/Ca(2+) exchanger to funnel Ca(2+) into the sarcoplasmic reticulum and minimize cytosolic [Ca(2+)] elevations that might otherwise contribute to hypertensive or proliferative vasculopathies.

Topics: Adenosine Triphosphate; Animals; Aorta; Calcium; Calcium Signaling; Cell Compartmentation; Cell Membrane; Clonazepam; Hypertension; Membrane Proteins; Mitochondria, Muscle; Mitochondrial Proteins; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Rats; Recombinant Fusion Proteins; Sarcoplasmic Reticulum; Sodium; Sodium-Calcium Exchanger; Thiazepines; Thiourea

The effects of endogenous angiotensin II (Ang II) and neuronal nitric oxide synthase (nNOS) on tonic sympathetic activity were studied in salt-sensitive hypertension-induced heart failure. Dahl salt-sensitive rats were fed 8% NaCl diet for 9 weeks to induce chronic heart failure (CHF-DSS). The effects of intravenous administration of a selective nNOS inhibitor, S-methyl-L: -thiocitrulline (SMTC), and an Ang II type 1-receptor blocker, losartan, on renal sympathetic nerve activity (RSNA) were examined in chronically instrumented conscious rats. Baroreceptor (baro)-unloaded RSNA was obtained by decreasing arterial pressure with caval occlusion to determine tonic RSNA. SMTC significantly decreased baro-unloaded RSNA, and subsequent losartan recovered baro-unloaded RSNA to the control level in CHF-DSS rats. To compare the effects of the inhibitors between low- and high-activity states of the renin-angiotensin system (RAS), Sprague-Dawley rats were fed low (0.04%)- or high (8%)-salt diets. A significant difference was found in the effects of SMTC and/or losartan on RSNA between the high- and low-RAS states, which suggested that there is a difference in the effect of endogenous Ang II on RSNA between salt-induced and other-type heart failure. To examine the effects of heart failure on brain-tissue nNOS activity, we measured the activities of the diencephalon in heart-failure rats. Heart failure significantly suppressed diencephalon nNOS activity, which was significantly different from the results in salt-sensitive hypertension without heart failure. These results suggest that endogenous Ang II has fewer effects, but nNOS has excitatory effects on tonic RSNA in salt-sensitive hypertension-induced heart failure.

Topics: Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Animals; Brain; Citrulline; Enzyme Inhibitors; Heart Failure; Hypertension; Kidney; Losartan; Male; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Pressoreceptors; Rats; Rats, Inbred Dahl; Renin-Angiotensin System; Sodium Chloride, Dietary; Sympathetic Nervous System; Thiourea

To elucidate the role of central neurons containing neuronal nitric oxide synthase (nNOS neurons) in the sympathetic nervous system in hypertensive Dahl salt-sensitive (DS) rats.. Dahl rats were fed either a regular-salt (0.4% NaCl) or high-salt (8% NaCl) diet for 4 weeks. The effect of intracerebroventricular administration of S-methyl-L-thiocitrulline, a selective nNOS inhibitor, on renal sympathetic nerve activity was examined in chronically instrumented conscious DS rats. The activity and protein amount of brain nNOS was evaluated by enzyme assay and western blot analysis. The distribution and number of nNOS neurons in the brainstem were examined immunohistochemically in hypertensive and normotensive DS rats.. S-methyl-L-thiocitrulline induced a larger increase in tonic renal sympathetic nerve activity generated before baroreflex-mediated inhibition in hypertensive DS rats than normotensive DS rats. Hypertensive DS rats showed increased nNOS activity in the brainstem, but not in the diencephalon or cerebellum. High nNOS activity was confirmed by an increase in the amount of nNOS protein. nNOS Neurons were localized in several nuclei throughout the brainstem; the dorsolateral periaqueductal gray, pedunculopontine tegmental nucleus, dorsal raphe nucleus, laterodorsal tegmental nucleus, lateral parabrachial nucleus, rostral ventrolateral medulla, nucleus tractus solitarius and raphe magnus. The number of nNOS neurons in these nuclei, except for the two raphes, was significantly greater in hypertensive than in normotensive DS rats.. These findings suggest that central nNOS-mediated sympathoinhibition may be enhanced in salt-sensitive hypertensive Dahl rats. The upregulated nNOS-mediated inhibition may occur in the central sympathetic control system generated before baroreflex-mediated inhibition.

Topics: Animals; Arginine; Citrulline; Enzyme Inhibitors; Hypertension; Immunohistochemistry; Injections, Intraventricular; Male; Medulla Oblongata; Nerve Tissue Proteins; Neural Inhibition; Neurons; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Pedunculopontine Tegmental Nucleus; Periaqueductal Gray; Raphe Nuclei; Rats; Rats, Inbred Dahl; Solitary Nucleus; Sympathetic Nervous System; Thiourea

Compared to sympathetic nervous system, the role of parasympathetic innervation on tone development, especially under diseased conditions, of the pulmonary artery is relatively unknown. In this study, the contractile effect of acetylcholine and the type(s) of muscarinic (M) receptor involved in the pulmonary artery (1st intralobar branch; endothelium-denuded, under resting tension) of the normotensive Wistar-Kyoto (WKY) and age-matched (male, 22-26 weeks old) Spontaneously hypertensive rats (SHR) were investigated. Cumulative administration of acetylcholine (> or =0.1 microM) caused a concentration-dependent increase in tension (antagonised by p-fluoro-hexahydro-sila-difenidol and 4-diphenylacetoxy-N-methylpiperidine, both are selective muscarinic M(3) receptor antagonists) and the magnitude of maximum contraction (expressed as % of 50 mM [K(+)](o)-induced contraction) was markedly enhanced in the presence of neostigmine (10 microM, an anti-cholinesterase) (acetylcholine 30 microM, SHR: 72% vs. 35%; WKY: 32% vs. 20%). In SHR only, acetylcholine-elicited contraction was suppressed by 1-[beta-[3-(4-Methoxyphenyl)-propoxyl]-4-methoxyphenethyl]-1H-imidazole (SK&F 96365, 1 microM), amiloride (500 microM), ethyl-isopropyl-amiloride (EIPA, 10 microM), 2-[2-[4-(4-Nitrobenzyloxy)phenyl]ethyl]isothiourea (KB-R 7943, 5 microM), 2,4-dichlorobenzamil (10 microM), and an equal molar substitution of [Na(+)](o) (< or =30 mM) with choline or N-methyl-D-glucamine. In nominally [Ca(2+)](o)-free, EGTA (0.5 mM)-containing Krebs' solution, acetylcholine (> or =3 microM) only elicited a small contraction. In conclusion, muscarinic M(3) receptor activation is responsible for the pulmonary artery contraction induced by acetylcholine, with a greater magnitude observed in SHR. The exaggerated contraction in SHR is probably due to an influx of [Na(+)](o) through the Na(+)/H(+) exchanger and the store-operated channels (SOC) into smooth muscle cells. Elevation of cytosolic [Na(+)](i) subsequently leads to an influx of [Ca(2+)](o) through the reverse mode of the Na(+)/Ca(2+) exchanger seems to play a permissive role in mediating the exaggerated contractile response of acetylcholine recorded in the SHR.

Topics: Acetylcholine; Amiloride; Animals; Calcium; Cholinesterase Inhibitors; Dose-Response Relationship, Drug; Endothelium, Vascular; Enzyme Inhibitors; Female; Hypertension; Imidazoles; In Vitro Techniques; Indoles; Male; Maleimides; Muscarinic Agonists; Muscarinic Antagonists; Neostigmine; Protein Kinase C; Pulmonary Artery; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, Muscarinic; Sodium; Sodium-Calcium Exchanger; Sodium-Hydrogen Exchangers; Sodium-Potassium-Exchanging ATPase; Species Specificity; Thiourea; Vasoconstriction; Vasodilator Agents

The present study was performed to evaluate the role of neuronal nitric oxide synthase (nNOS)-derived nitric oxide (NO) during the developmental phase of hypertension in transgenic rats harboring the mouse Ren-2 renin gene (TGR). The first aim of the present study was to examine nNOS mRNA expression in the renal cortex and to assess the renal functional responses to intrarenal nNOS inhibition by S-methyl-L-thiocitrulline (L-SMTC) in heterozygous TGR and in age-matched transgene-negative Hannover Sprague-Dawley rats (HanSD). The second aim was to evaluate the role of the renal sympathetic nerves in mediating the renal functional responses to intrarenal nNOS inhibition. Thus, we also evaluated the effects of intrarenal L-SMTC administration in acutely denervated TGR and HanSD. Expression of nNOS mRNA in the renal cortex was significantly increased in TGR compared with HanSD. Intrarenal administration of L-SMTC decreased the glomerular filtration rate (GFR), renal plasma flow (RPF) and sodium excretion and increased renal vascular resistance (RVR) in HanSD. In contrast, intrarenal inhibition of nNOS by L-SMTC did not alter GFR, RPF or RVR and elicited a marked increase in sodium excretion in TGR. This effect of intrarenal L-SMTC was not observed in acutely denervated TGR. These results suggest that during the developmental phase of hypertension TGR exhibit an impaired renal vascular responsiveness to nNOS derived NO or an impaired ability to release NO by nNOS despite enhanced expression of nNOS mRNA in the renal cortex. In addition, the data indicate that nNOS-derived NO increases tubular sodium reabsorption in TGR and that the renal nerves play an important modulatory role in this process.

Topics: Analysis of Variance; Animals; Animals, Genetically Modified; Citrulline; Denervation; Enzyme Inhibitors; Gene Expression Regulation; Hypertension; Kidney; Male; Matched-Pair Analysis; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Rats; Rats, Inbred Strains; Renal Circulation; Renin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sympathetic Nervous System; Thiourea

Lead-induced hypertension has previously been shown to be closely associated with an increase in reactive oxygen species in low lead (100 ppm)-treated rats. The present study has attempted to define the specific moiety involved by noting the blood pressure (BP), reactive oxygen species (MDA-TBA), hydroxyl radical, and nitrotyrosine responses to infusion of the reactive oxygen species scavenger dimethylthiourea. Dimethylthiourea, a reputed scavenger of hydroxyl radical, normalized BP and MDA-TBA in the lead-treated rats but had no effect in normal control animals. MDA-TBA, hydroxyl radical, and nitrotyrosine, the tissue end product of peroxynitrite, were reduced to or toward normal by dimethylthiourea. The results, therefore, are consistent with the suggestion that either hydroxyl radical or peroxynitrite may be the reactive species affected by lead.

Topics: Animals; Blood Pressure; Free Radical Scavengers; Hydroxyl Radical; Hypertension; Lead; Lipid Peroxides; Male; Rats; Rats, Sprague-Dawley; Thiourea; Tyrosine

This study was designed to determine the influence of neuronal nitric oxide synthase (nNOS) in tubular flow-dependent regulation of afferent arteriolar diameter in hypertensive Sprague-Dawley rats that received 60 ng/min angiotensin II (Ang II) subcutaneously for 13 days. Systolic blood pressure of control and Ang II-infused rats averaged 122+/-2 (n=23) and 194+/-2 mm Hg (n=24). Afferent arteriolar responses to the nNOS inhibitor S-methyl-L-thiocitrulline (L-SMTC; 0.1 to 10 micromol/L) and the nonselective NOS inhibitor Nomega-nitro-L-arginine (L-NNA; 1 to 100 micromol/L) were assessed in vitro using the blood-perfused juxtamedullary nephron preparation. At a perfusion pressure of 160 mm Hg, afferent arteriolar diameters from control and Ang II-infused rats averaged 18.7+/-1.1 microm (n=8) and 18.1+/-1.1 microm (n=9), respectively, and decreased by 19. 9+/-1.5% and 11.8+/-1.1%, respectively, in response to 10 micromol/L L-SMTC. The L-SMTC-induced afferent arteriolar constriction was significantly greater in control than in Ang II-infused rats. In contrast, 100 micromol/L L-NNA constricted afferent arterioles similarly in both control (n=8) and Ang II-infused (n=7) rats. After transection of the loops of Henle to interrupt flow to the macula densa, the vasoconstrictor responses to L-SMTC but not to L-NNA were reversed. Increasing distal volume delivery by addition of 10 mmol/L acetazolamide to the blood perfusate significantly enhanced the afferent arteriolar constrictor responses to 10 micromol/L L-SMTC (34.5+/-4.8%, n=7) in normotensive rats. In contrast, in Ang II-infused rats, acetazolamide treatment did not enhance the responses to L-SMTC (n=8). These results indicate that chronic Ang II infusion reduces the ability of nNOS-derived nitric oxide to counteract the afferent arteriolar response to increased distal tubular flow.

Topics: Acetazolamide; Angiotensin II; Animals; Arterioles; Blood Pressure; Citrulline; Enzyme Inhibitors; Hypertension; Juxtaglomerular Apparatus; Kidney Medulla; Male; Microscopy, Video; Muscle, Smooth, Vascular; Nephrons; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Nitroarginine; Rats; Rats, Sprague-Dawley; Thiourea; Vasoconstriction; Vasodilation

Earlier studies have demonstrated increased oxygen free radical (OFR) activity, diminished antioxidant capacity and reduced OFR-inactivating enzymes in chronic renal failure (CRF). Via inactivation of nitric oxide (NO), oxidation of arachidonic acid and a direct vasoconstrictive action, OFR can potentially raise blood pressure (BP). This study was designed to test the hypothesis that increased OFR activity may contribute to CRF hypertension. Four weeks after 5/6 nephrectomy rats were treated for two weeks with either lazaroid, a potent antioxidant and lipid peroxidation inhibitor (CRF-LZ group), or vehicle alone (CRF group) by daily gastric gavage. The control group was sham operated and placebo treated. The CRF group exhibited significant increases in BP and plasma lipid peroxidation product, malondialdehyde (MDA), indicating enhanced OFR activity. This was accompanied by decreased urinary nitrate/nitrite (NOx) excretion suggesting depressed NO production. LZ therapy normalized plasma MDA and significantly ameliorated CRF-induced hypertension. Both MDA and blood pressure (BP) rose to values seen in the untreated CRF group within two weeks after termination of LZ therapy. Intravenous administration of the hydroxyl radical scavenger, dimethylthiourea (DMTU), significantly lowered BP and raised urinary NOx excretion. However, no discernible effects were found with either superoxide dismutase or catalase (superoxide and H2O2 quenchers). The results suggest that increased OFR activity is, in part, responsible for CRF-associated HTN. The study further points to hydroxyl radicals as the major source of OFR in CRF animals. If substantiated in humans, antioxidant therapy becomes a logical adjunct in the management of CRF.

Topics: Animals; Antioxidants; Blood Pressure; Free Radical Scavengers; Hypertension; Kidney Failure, Chronic; Male; Malondialdehyde; Nitrites; Pregnatrienes; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Superoxide Dismutase; Thiourea; Uremia

Our previous results demonstrate the occurrence of presynaptic inhibitory histamine H3 receptors on sympathetic neurons innervating resistance vessels of the pithed rat. The present study, in which new H3 receptor ligands with increased potency and selectivity (imetit, clobenpropit) were used, was designed to further explore the role of H3 receptors in the regulation of the rat cardiovascular system. In particular we were interested whether these receptors may be activated by endogenous histamine and whether they are detectable in an experimental model of hypertension. All experiments were performed on pithed and vagotomized rats treated with rauwolscine 1 mumol/kg. In normotensive Wistar rats the electrical (1 Hz, 1 ms, 50 V for 20 s) stimulation of the preganglionic sympathetic nerve fibres increased diastolic blood pressure by about 35 mmHg. Two H3 receptor agonists, R-(-)-alpha-methylhistamine and imetit, inhibited the electrically induced increase in diastolic blood pressure in a dose-dependent manner. The maximal effect (about 25%) was obtained for R-(-)-alpha-methylhistamine at about 10 mumol/kg and for imetit at about 1 mumol/kg. Two H3 receptor antagonists, thioperamide 1 mumol/kg and clobenpropit 0.1 mumol/kg, attenuated the inhibitory effect of imetit. The neurogenic vasopressor response was increased by about 15% by thioperamide 1 mumol/kg and clobenpropit 0.1 mumol/kg and decreased by 25% by the histamine methyltransferase inhibitor metoprine 37 mumol/kg. R-(-)-alpha-Methylhistamine, imetit, thioperamide, clobenpropit and metoprine did not affect the vasopressor response to exogenously added noradrenaline 0.01 mumol/kg (which increased diastolic blood pressure by about 40 mmHg). Metoprine had only a very low affinity for H3 binding sites (labelled by 3H-N alpha-methylhistamine; pKi 4.46). In pithed Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats, electrical (1 Hz, 1 ms, 50 V for 10 s) stimulation increased diastolic blood pressure by 28 and 37 mmHg, respectively. Imetit inhibited the neurogenic vasopressor response to about the same extent in WKY and SHR rats (maximal effect of about 30%). The inhibitory influence of imetit was diminished by thioperamide 1 mumol/kg to about the same degree in rats of either strain. The present study confirms the occurrence of presynaptic H3 receptors on sympathetic nerve fibres involved in the inhibition of the neurogenic vasopressor response. Moreover, it demonstrates that these H3 receptors are

Topics: Adrenergic Fibers; Animals; Blood Pressure; Decerebrate State; Electric Stimulation; Histamine; Histamine Agonists; Histamine Antagonists; Hypertension; Imidazoles; Male; Methylhistamines; Piperidines; Pyrimethamine; Rats; Rats, Wistar; Receptors, Histamine H3; Thiourea; Vagotomy; Vascular Resistance

Topics: Arginine Vasopressin; Disease; Epinephrine; Hexamethonium; Hypertension; Rats; Rodent Diseases; Thiourea; Vasoconstrictor Agents; Vasopressins

Topics: Angiotensins; Anti-Bacterial Agents; Humans; Hypertension; Norepinephrine; Thiourea; Vasoconstrictor Agents

Topics: Cell Nucleus; Humans; Hypertension; Thiouracil; Thiourea