vasoactive-intestinal-peptide and Hypertension

Hypertension management poses a major challenge to clinicians globally once non-drug (lifestyle) measures have failed to control blood pressure (BP). Although drug treatment strategies to lower BP are well described, poor control rates of hypertension, even in the first world, suggest that more needs to be done to surmount the problem. A major issue is non-adherence to antihypertensive drugs, which is caused in part by drug intolerance due to side effects. More effective antihypertensive drugs are therefore required which have excellent tolerability and safety profiles in addition to being efficacious. For those patients who either do not tolerate or wish to take medication for hypertension or in whom BP control is not attained despite multiple antihypertensives, a novel class of interventional procedures to manage hypertension has emerged. While most of these target various aspects of the sympathetic nervous system regulation of BP, an additional procedure is now available, which addresses mechanical aspects of the circulation. Most of these new devices are supported by early and encouraging evidence for both safety and efficacy, although it is clear that more rigorous randomized controlled trial data will be essential before any of the technologies can be adopted as a standard of care.

Topics: Angiotensin Receptor Antagonists; Antihypertensive Agents; Arteriovenous Shunt, Surgical; Baroreflex; Catheter Ablation; Clinical Trials as Topic; Deep Brain Stimulation; Elapid Venoms; Evidence-Based Medicine; Forecasting; Humans; Hypertension; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, C-Type; Neprilysin; Nerve Regeneration; Norepinephrine; Peptides; Renin-Angiotensin System; Sympathectomy; Transcutaneous Electric Nerve Stimulation; Vasoactive Intestinal Peptide

The biological clock, the suprachiasmatic nucleus (SCN), is essential for our daily well-being. It prepares us for the upcoming period of activity by an anticipatory rise in heart rate, glucose and cortisol. At the same time the 'hormone of the darkness', melatonin, decreases. Thus, the time-of-day message penetrates into all tissues, interestingly not only by means of hormones but also by a direct neuronal influence of the SCN on the organs of the body. The axis between the SCN and the paraventricular nucleus of the hypothalamus (PVN) is crucial for the organization/synchronization of the neuroendocrine and autonomic nervous system with the time of day. This SCN-neuroendocrine PVN axis takes care of a timely hormonal secretion. At the same time, the SCN-autonomic PVN axis fine-tunes the organs by means of the autonomic nervous system for the reception of these hormones. Finally, the similar organization of the projections of the human SCN as compared with that in the rodent brain suggests that these basic principles of neuroendocrine autonomic interaction may also be true in the human. The physiological data collected in humans thus far seem to support this hypothesis, while pathological changes in the SCN of humans suffering from depression or hypertension indicate a role for the SCN in the etiology of these diseases.

Topics: Animals; Autonomic Nervous System; Behavior; Biological Clocks; Circadian Rhythm; Depression; gamma-Aminobutyric Acid; Humans; Hypertension; Mammals; Pituitary Hormones; Suprachiasmatic Nucleus; Vasoactive Intestinal Peptide; Vasopressins

Cerebral capillary endothelium forms a barrier limiting and controlling the movement of ions and solutes between blood and brain. Recent anatomical, physiological and biochemical studies have suggested the possibility that capillary function may be directly controlled by neuronal structures. Alterations in neuronal systems involved in the regulation of microcirculation may account for microvascular dysfunctions which occur in different pathologic conditions.

Topics: Acetylcholine; Aging; Animals; Biological Transport, Active; Blood-Brain Barrier; Brain; Capillaries; Capillary Permeability; Cerebrovascular Circulation; Cholecystokinin; Diabetes Mellitus; Dopamine; Endothelium; Histamine; Hypertension; Hypoxia, Brain; Locus Coeruleus; Microcirculation; Neural Pathways; Neurons; Norepinephrine; Receptors, Neurotransmitter; Serotonin; Substance P; Vasoactive Intestinal Peptide

Polypeptides are endogenous agents, involved in the regulation of many physiologic functions and the pathogenesis of several diseases. Polypeptide antagonists form a group of new chemical entities which may provide valid therapeutic agents. Some polypeptides (angiotensin, kinins) are released through the action of proteolytic enzymes (renin, kallikreins) and act as hormones or autacoids; others (substance P, neurotensin) are synthetized by nervous cells to serve as neurotransmitters or neuromodulators. The main homeostatic role of the renin-angiotensin system is to uphold high systemic arterial blood pressure. Overproduction of renin and insufficient checking of renin secretion are among the most common causes of arterial hypertension. Several forms of arterial hypertension (neurovascular, idiopathic) benefit from a reduction in renin-angiotensin system activity. This is achieved either through decreasing renin secretion, by inhibiting conversion of angiotensin I into angiotensin II, or through blocking the peripheral actions (at the receptor sites) of angiotensin II. Renin secretion is very significantly reduced by beta-blocking agents (propranolol); conversion of angiotensin I into angiotensin II is inhibited by teprotide, captopril and their derivatives; peripheral actions of angiotensin II are blocked by saralasin. Bradykinin and related agents produce vasodilation, increase vascular permeability and stimulate pain fibers. Kinins thus reproduce the cardinal features of inflammation and are held to be mediators of the inflammatory reaction. The substance P neuropeptide is found in the brain and bowel; it may act as a transmitter of the sensation of pain at the spinal cord and central nervous system sites. Among other effects outside of the brain, substance P is a potent vasodilator and inhibits renin secretion. Neurotensin is a neuropeptide which produces hypothermia, muscular relaxation and analgesia. Outside of the brain, this peptide is involved in the regulation of gastric secretion, intestinal motility and insulin and glucagon secretion. The vasoactive intestinal peptide, found in certain cholinergic nerve endings, is a large peptide which inhibits gastric secretion, intestinal motility and vascular tone.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Captopril; Humans; Hypertension; Inflammation; Kallikreins; Kinins; Neurotensin; Peptides; Renin-Angiotensin System; Substance P; Vasoactive Intestinal Peptide

Topics: Animals; Brain; Carbon Dioxide; Central Nervous System; Cerebrovascular Circulation; Homeostasis; Humans; Hypertension; In Vitro Techniques; Intracranial Arteriosclerosis; Intracranial Pressure; Neural Pathways; Oxygen; Parasympathetic Nervous System; Reflex; Sympathetic Nervous System; Vasoactive Intestinal Peptide; Vasodilation

In elderly subjects blood pressure (BP) may fall after a meal. The mechanism of this phenomenon is unknown, but it has been suggested that it may be mediated by insulin and/or vasoactive gut hormones. We studied in normo- and hypertensive elderly subjects the effects of the synthetic long-acting somatostatin analog octreotide (SMS 201-995) on the BP reduction that follows oral glucose administration in subjects who are recumbent and on their postglucose plasma vasoactive intestinal polypeptide (VIP) and insulin concentrations. After placebo treatment, mean arterial pressure fell by 15 +/- 1 mm Hg (P less than 0.001) in the 10 hypertensive subjects and by 7 +/- 2 mm Hg (P less than 0.01) in the 10 normotensive subjects. In contrast, when 50 micrograms octreotide were given sc, BP did not change significantly in either group. Oral glucose did not induce a rise in plasma VIP after either octreotide or placebo administration. The postglucose rises in plasma glucose concentrations were similar after octreotide and placebo treatments in both groups. After placebo administration the postglucose plasma insulin levels increased from 79 to 519 pmol/L in the hypertensive subjects and from 63 to 464 pmol/L in the normotensive subjects, whereas after octreotide treatment plasma insulin increased little in either group. These data indicate that treatment with octreotide holds promise for patients with symptomatic postprandial hypotension, and that VIP does not seem to play a role in this phenomenon.

Topics: Administration, Oral; Aged; Aged, 80 and over; Blood Glucose; Blood Pressure; Female; Glucose; Heart Rate; Humans; Hypertension; Insulin; Male; Octreotide; Vasoactive Intestinal Peptide

Introduction: Chronic obstructive pulmonary disease (COPD) with hypertension occupy a leading position in morbidity and mortality in the world. The question of studying a single pathological way of their development, the search for diagnostic markers and therapeutic targets in this comorbid pathology remains relevant. The aim of the study was to study cardiopulmonary parameters in patients with chronic obstructive pulmonary disease with concomitant hypertension, depending on the level of vasoactive intestinal peptide (VIP).. Materials and methods: 99 patients with COPD GOLD 2 were examined, 54 of whom had concomitant hypertension II stage, in which the dependence of lipid metabolism, spirometry and hemodynamic parameters, depending on the level of VIP in blood serum.. Results and conclusions: It was established that the smallest values of VIP and the greatest changes in cardiopulmonary parameters, lipid metabolism were found in the cohort of persons with concomitant hypertension. There was a significant decrease in spirometry values and an increase in hemodynamic parameters, respectively, a decrease in VIP levels in patients with COPD in combination with hypertension, which may indicate its role in the formation of these pathologies due to a decrease in its protective function, both in relation to apoptosis of alveolar cells and in relation to progression atherosclerosis and high blood pressure. It was also noted that in patients with the lowest VIP serum levels, a more rapid formation of COPD was observed. The data obtained make it possible to consider VIP as a diagnostic marker and a potential therapeutic target for the comorbid pathology examined.

Topics: Disease Progression; Humans; Hypertension; Pulmonary Disease, Chronic Obstructive; Vasoactive Intestinal Peptide

Chronic watery diarrhoea can be a presentation of gastrointestinal disease itself or a less-evident systemic disease. A 17-month-old boy presented with intractable diarrhoea, failure to gain weight, refractory tachycardia and severe hypertension. The ability to recognise and make a quick diagnosis of secretory type of diarrhoea dictated the outcome of patients with this ailment. Catecholamine hypersecretion was considered with the additional clues of refractory tachycardia and hypertension, a well-recognised phenomenon of neuroblastic tumours. A neuroblastic tumour can lead to vasoactive intestinal peptide (VIP) overexpression, which may result in secretory diarrhoea. In this situation, measurements of plasma VIP enabled crucial diagnosis. Imaging studies were used to identify and localise a neuroblastic tumour. Subsequent removal of the tumour was curative and led to the resolution of the symptoms.

Topics: Adrenal Gland Neoplasms; Catecholamines; Diarrhea; Humans; Hypertension; Infant; Male; Neuroblastoma; Tachycardia; Treatment Outcome; Vasoactive Intestinal Peptide

Hypertensive rats with multiple extra copies of the renin gene (TGR) exert an inverted circadian blood pressure (BP) profile. We investigated whether circadian oscillations in the hypothalamic suprachiasmatic nucleus (SCN), a main circadian oscillator, and the paraventricular nucleus (PVN), involved in BP control, are influenced in TGR rats. The expression of the clock gene per1, a marker of circadian timing, was measured in the SCN and PVN. Moreover, the expression of genes encoding vasopressin (AVP), vasoactive intestinal peptide (VIP) in the SCN, and AVP and oxytocin (OXT) in the PVN were studied by in situ hybridization. Expression of the per1 gene showed a distinct circadian rhythm in both the SCN and PVN with no differences observed between the TGR and control Sprague–Dawley (SD) rats. The expression of avp in the SCN was rhythmic in both strains and moderately higher in TGR than in SD rats while no significant changes were found in the PVN. The expression of vip in the SCN and oxt in the PVN did not differ between both strains. Our results may indicate that changes occurring downstream to the SCN are responsible for the development of the inverted BP rhythm in TGR hypertensive rats.

Topics: Animals; Arginine Vasopressin; Autoradiography; Blood Pressure; Circadian Rhythm; Gene Expression Regulation; Heart Rate; Hypertension; Motor Activity; Oxytocin; Paraventricular Hypothalamic Nucleus; Period Circadian Proteins; Rats; Rats, Sprague-Dawley; RNA, Messenger; Signal Transduction; Suprachiasmatic Nucleus; Vasoactive Intestinal Peptide

We examined morphological characteristics of the carotid body of spontaneously hypertensive rats (SHR), those of age-matched normotensive Wistar rats (NWR), and age-matched genetically comparable Wistar Kyoto rats (WKY). We examined the distribution and abundance of four different regulatory neuropeptides: substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), and neuropeptide Y (NPY) in the carotid bodies of these three strains of rats. The carotid bodies of SHR were larger than those of NWR and WKY. The values of the long axis of the carotid bodies of SHR were significantly larger (1.3 times) than those of NWR and WKY. In the carotid bodies of SHR, the percentage of relatively large vessels was similar to that of the carotid bodies of WKY, although the carotid bodies themselves were significantly larger than in WKY. The density of VIP varicose fibers in the carotid bodies of SHR was lower than in the carotid bodies of WKY, although the density of SP, CGRP and NPY fibers was similar to that of the carotid bodies of NWR and WKY. These findings suggested that VIP was unrelated to enlargement of the carotid body of SHR, but it might modify the sensitivity of chemoreceptors in the carotid body.

Topics: Animals; Calcitonin Gene-Related Peptide; Carotid Body; Coloring Agents; Eosine Yellowish-(YS); Hematoxylin; Hypertension; Immunohistochemistry; Male; Nerve Fibers; Neuropeptide Y; Neuropeptides; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Rats, Wistar; Species Specificity; Substance P; Tyrosine 3-Monooxygenase; Vasoactive Intestinal Peptide

A variety of studies has linked vasoactive intestinal peptide (VIP) to idiopathic pulmonary arterial hypertension (IPAH). In this study, we investigated the correlation between VIP gene variants and IPAH in Chinese population. A total of 81 consecutive unrelated patients diagnosed as IPAH from 2006 to 2008 and 250 controls were included in the study. VIP gene variants were screened by direct sequencing, and VIP serum level was determined by enzyme-linked immunosorbent assay. Clinical and hemodynamic data of all patients were also obtained. The variant g.8129T-->C in exon 7 was found to be the only variant in the coding region of VIP gene with a significantly higher frequency in patients (40.7%) than in control samples (15.2%). Moreover, there was marked difference in VIP serum level and hemodynamic data between IPAH patients with and without the variant. The variant g.8129T-->C in exon 7 of VIP gene was correlated with the clinical phenotype of lower VIP serum level, higher mean pulmonary artery pressure and pulmonary vascular resistance in patients with IPAH comparing to those in patients without this variant. The VIP gene variant g.8129T-->C may be one of the risk factors in the pathogenesis of IPAH.

Topics: Adolescent; Adult; Asian People; Child; China; Female; Genetic Variation; Hemodynamics; Humans; Hypertension; Male; Middle Aged; Point Mutation; Pulmonary Artery; Sequence Analysis, DNA; Vasoactive Intestinal Peptide

To report a case of a pheochromocytoma secreting vasoactive intestinal peptide (VIP).. We studied a 77-year-old woman who had suffered from persistent diarrhea and episodes of sweating and palpitations.. She had neither previous or current anamnesis of hypertension nor any known familial dispositions to endocrine diseases. Initially gastrointestinal investigations were carried out based on longstanding diarrhea with hypopotassemia, but radiological imaging revealed a unilateral adrenal mass. Biochemical testing showed increased levels of catecholamine and VIP, and (123)I-metaiodobenzylguanidine scintigraphy confirmed the adrenal origin as well as the diagnosis of a VIP-producing pheochromocytoma. The patient underwent surgical removal of the tumor which led to relief of symptoms and normalized laboratory values.. This case report focuses on the protean mode of presentation seen in pheochromocytomas as well as their capacity to produce several neuropeptides, ultimately intensifying the need for early examination for this condition despite unrelated symptoms.

Topics: Adrenal Gland Neoplasms; Aged; Catecholamines; Female; Humans; Hypertension; Pheochromocytoma; Vasoactive Intestinal Peptide

We determined whether a single intratracheal and subcutaneous administration of biocompatible and biodegradable vasoactive intestinal peptide self-associated with sterically stabilized liposomes (VIP-SSL) normalizes mean arterial pressure (MAP) in spontaneously hypertensive hamsters (SHH). We found that VIP-SSL (0.1 nmol) administered by either routes normalizes MAP (p < 0.05). Maximal effect was observed within 10-20 min and lasted for 6 h. VIP-SSL had no significant effects on heart rate. VIP alone (0.1 nmol) and empty SSL had no significant effects on MAP. VIP-SSL (0.1 nmol) had no significant effects on MAP and heart rate in age/genetically-matched control hamsters. Given these data, we suggest that pulmonary and subcutaneous delivery of VIP-SSL should be further developed as peptide nanomedicine for essential hypertension.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Cricetinae; Hypertension; Injections, Subcutaneous; Intubation, Intratracheal; Liposomes; Male; Vasoactive Intestinal Peptide

We have previously shown that self-association of human vasoactive intestinal peptide with sterically stabilized liposomes (VIP-alpha) alters peptide conformation from random coil in aqueous solution to alpha-helix. This, in turn, protects the peptide from hydrolysis and amplifies and prolongs its bioactivity. The purpose of this study was to determine whether a single, intravenous injection of low-dose human VIP-alpha normalizes systemic arterial pressure in anesthetized spontaneously hypertensive hamsters for a prolonged period of time in a selective fashion. We found that intravenous injection of human VIP-alpha, VIP alone (each, 1.0 nmol) and empty liposomes had no significant effects on mean arterial pressure (MAP) in normotensive hamsters. By contrast, human VIP-alpha (0.01-1.0 nmol) evoked a significant concentration-dependent decrease in MAP to the normative range in spontaneously hypertensive hamsters that lasted throughout the observation period (6 h; p<0.05). VIP alone and empty liposomes had no significant effects on MAP in these animals. We conclude that a single, low-dose intravenous injection of human VIP-alpha normalizes systemic arterial pressure in spontaneously hypertensive hamsters for a prolonged period of time in a selective fashion. We suggest that human VIP-alpha should be further developed as a long-acting, biocompatible and biodegradable peptide nanomedicine for essential hypertension.

Topics: Animals; Antihypertensive Agents; Biocompatible Materials; Biodegradation, Environmental; Cricetinae; Humans; Hypertension; Injections, Intravenous; Male; Nanostructures; Vasoactive Intestinal Peptide

We have shown previously that the concentration of Vasoactive Intestinal Peptide (VIP) in the heart is inversely correlated with the degree of fibrosis in a number of experimental models of early myocardial fibrosis. Vasopeptidase inhibition and angiotensin converting enzyme inhibition both decrease myocardial fibrosis. In this study, we sought to determine whether this myocardial protective effect might reflect increased VIP concentrations in the heart. We compared the effects of 4 weeks treatment of the vasopeptidase inhibitor omapatrilat and the angiotensin converting enzyme inhibitor enalapril on the degree of fibrosis and the concentration of VIP in the heart in salt sensitive hypertension induced by treatment with L-nitro-omega-methylarginine (L-NAME). Systolic blood pressure decreased in both treatment groups compared with control (omapatrilat P<0.005; enalapril P<0.001). Myocardial fibrosis was less for omapatrilat than control (P<0.0005) and enalapril (P<0.0005) groups. Myocardial VIP was greater in omapatrilat than in controls (P<0.005) and enalapril-treated rats (P<0.05). We conclude that vasopeptidase inhibition exerts a greater myocardial protective effect than angiotensin converting enzyme inhibition. Further, this myocardial protective effect is associated with increased VIP in the heart suggesting a pathogenetic role for VIP depletion in the development of fibrosis in the heart.

Topics: Animals; Enalapril; Fibrosis; Hypertension; Male; Myocardium; Peptide Hydrolases; Protease Inhibitors; Pyridines; Rats; Rats, Inbred WKY; Thiazepines; Vasoactive Intestinal Peptide

To investigate the expression of vasoactive intestinal peptide (VIP) and substance P (SP) in the cochlea of spontaneously hypertensive rat (SHR), and to assess the function of VIP and SP in the cochlea following the damage of hypertension, hearing thresholds of ABR were observed and the fixative (4% paraformaldehyde) was pumped through the circulatory system. Adult Wistar rats (3 months, n=20) served as the control group and SHRs (3 months, n=20) as the hypertension group. Bullas were taken out and cochleas were irrigated in vitro with the same fixative. The number of base turn's spiral ganglions in the sections was counted. The expression of VIP and SP were detected by SABC method and the images of the sections were analyzed. The number of base turn's spiral ganglsons in the hypertension group was significantly less than in the normal group (P<0.01). VIP and SP were expressed in the spiral ganglion cytoplasma and stria vascularis of the two groups. There were no significant difference in the expression of VIP and SP in spiral ganglion cytoplasma (P>0.05) between the two groups. However, in stria vascularis the expression of VIP in the hypertension group was higher than in the normal group (P<0.05), and no significant difference in SP was found between the two groups. It was suggested that VIP not only contributed to the regulation of the cochlea microcirculation, but also made the neurotransmitter in the pathway of the auditory system. However, SP made only the neurotransmitter in the pathway of the auditory system.

Topics: Animals; Cochlea; Hypertension; Rats; Rats, Inbred SHR; Rats, Wistar; Substance P; Vasoactive Intestinal Peptide

To investigate the expression of vasoactive intestinal peptide (VIP) and substance P (SP) in the cochlea of spontaneously hypertensive rat (SHR) and normal rat, and to evaluate the function of VIP and SP in the cochlea following the damage of hypertension.. The expression of VIP and SP in the cochlea of SHR was studied by immunohistochemical staining, and the mean optical density (OD) values of the positive fields were quantitatively examined by image analysis system.. The number of spiral ganglion cells at base turn in the hypertension group was significantly less than the normal (P < 0.01). VIP was expressed in the spiral ganglion cell plasm and stria vascularis of rats, so did SP. In spiral ganglion cell plasm the expression of VIP and SP had no significant difference between the two groups (P > 0.05); in stria vascularis the expression of VIP of the hypertension group was higher than the normal (P < 0.05). However, no significant difference in SP was found between the two groups.. VIP not only contributes to regulate the cochlea microcirculation, but also acts as the neurotransmitter in the pathway of the auditory system. However, SP may be only a neurotransmitter in the pathway of the auditory system.

Topics: Animals; Cochlea; Female; Hypertension; Labyrinth Diseases; Male; Rats; Rats, Inbred SHR; Rats, Wistar; Substance P; Vasoactive Intestinal Peptide

Ganglioneuromas (GNs) are neural crest cell-derived tumors and rarely occur in the adrenal gland. There are presently no markers that can reliably distinguish benign and malignant neuroendocrine tumors. Here we describe a 63-year-old woman who developed sudden chest pain and hypertension combined with increased stool frequency. An incidental adrenal mass 5 cm in size with a bright signal on T2-weighted magnetic resonance imaging was discovered. Biochemical evaluation and (131)I-metaiodobenzylguanidine (MIBG) scintigraphy were negative. Histopathological examination revealed a mature adrenal GN. Neuroblastoma, the immature form of a GN, is known for deletions on chromosomal locus 1p36, and adrenal tumors frequently show allele loss on 17p. To further elucidate the histo- and pathogenesis of adrenal GN, we performed loss of heterozygosity studies on chromosomal loci 1p34-36 and 17p13 (the p53 gene locus) after careful microdissection of tumor and normal tissue. We did not detect allelic losses at these loci with the informative polymorphic markers used, suggesting that these loci are not involved in tumorigenesis. In addition, immunohistochemical investigation of the GN was positive for vasoactive intestinal peptide, a hormone commonly expressed in ganglion cells. We suggest that in our patient with an adrenal GN, the combination of biochemical, scintigraphic, molecular, immunohistochemical, and histopathological findings are all consistent with the benign morphology of this tumor.

Topics: Adrenal Gland Neoplasms; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 17; Diarrhea; Female; Ganglioneuroma; Humans; Hypertension; Immunoenzyme Techniques; Loss of Heterozygosity; Magnetic Resonance Imaging; Middle Aged; Vasoactive Intestinal Peptide

Abnormalities in autonomic activity resulting in disturbances of the diurnal rhythm of many physiologic processes were recently revealed in hypertensive patients. These findings suggest deteriorations in the functioning of the suprachiasmatic nucleus (SCN), which is known to be the biological clock of mammals. To test this hypothesis, we carried out an immunocytochemical study of the SCN of primary hypertension patients who had died due to myocardial infarction or brain hemorrhage, and compared them with those of individuals with a normal blood pressure who had never had any autonomic disturbances and died from myocardial infarction after chest trauma or from hypothermia. We found that the staining for the three main neuronal populations of the SCN; i.e., vasopressin, vasoactive intestinal polypeptide, and neurotensin, reduced by more than 50% in the hypertensives compared with controls. The present data indicate a serious dysregulation of the biological clock in hypertensive patients. Such a disturbance may cause a harmful hemodynamic imbalance with a negative effect on circulation, especially in the morning, when the inactivity-activity balance changes. The difficulty in adjusting from inactivity to activity might be involved in the morning clustering of cardiovascular events.

Topics: Adult; Aged; Blood Pressure; Chronobiology Disorders; Circadian Rhythm; Female; Humans; Hypertension; Male; Middle Aged; Neuropeptides; Neurotensin; Suprachiasmatic Nucleus; Vasoactive Intestinal Peptide; Vasopressins

The purpose of this study was to determine whether activation of prostaglandin H(2)-thromboxane A(2) (PGH(2)-TxA(2)) receptors impedes vasodilation in the in situ peripheral microcirculation of spontaneously hypertensive hamsters, a new rodent model of high-renin genetic hypertension. Using intravital microscopy, we found that vasodilation elicited by suffusion of acetylcholine and vasoactive intestinal peptide (VIP), two neurotransmitters localized in perivascular nerves in the peripheral circulation, on the in situ cheek pouch was significantly attenuated in spontaneously hypertensive hamsters relative to age- and genetically matched normotensive hamsters (P < 0.05). However, nitroglycerin-induced vasodilation was similar in both groups. Pretreatment with SQ-29548, a selective and potent PGH(2)-TxA(2)-receptor antagonist, restored acetylcholine- and VIP-induced vasodilation in spontaneously hypertensive hamsters. SQ-29548 had no significant effects on resting arteriolar diameter and on nitroglycerin-induced vasodilation in both groups. SQ-29548 slightly but significantly potentiated VIP- but not acetylcholine-induced vasodilation in normotensive hamsters. Collectively, these data indicate that activation of PGH(2)-TxA(2) receptors impedes agonist-induced vasodilation in the in situ cheek pouch of spontaneously hypertensive hamsters. We suggest that this model is suitable for studying the role of prostanoids in mediating vasomotor dysfunction observed in genetic hypertension.

Topics: Acetylcholine; Animals; Bridged Bicyclo Compounds, Heterocyclic; Cheek; Cricetinae; Fatty Acids, Unsaturated; Hydrazines; Hypertension; Male; Nitroglycerin; Prostaglandin H2; Prostaglandins H; Thromboxane A2; Vasoactive Intestinal Peptide; Vasodilation; Vasodilator Agents; Vasomotor System

Topics: Adult; Humans; Hypertension; Hypertrophy, Left Ventricular; Insulin; Middle Aged; Vasoactive Intestinal Peptide

The effects of repeated sensory stimulation (electro-acupuncture) and physical exercise (running) on open-field behaviour and on hippocampal concentrations of neuropeptide Y, neurokinin A, substance P, galanin and vasoactive intestinal peptide (VIP)-like immunoreactivities were studied in WKY (wistar-Kyoto) and SHR (spontaneously hypertensive) rats. Significantly higher concentrations of substance P-like immunoreactivity, neurokinin A-like immunoreactivity and neuropeptide Y-like immunoreactivity were found in the hippocampus immediately after 3 weeks of treatment (electro-acupuncture and running), but not 1 week after the last (tenth) changes in neuropeptide concentrations were similar in the two rat strains. Open-field behaviour was significantly reduced during the treatment period in both strains. There were significant negative correlations between behaviour and neuropeptide concentrations in SHR rats, suggesting interdependency with sympathetic activity. It is proposed that the effects of electro-acupuncture and physical exercise in rats are related to increases in neuropeptide Y, neurokinin A and substance P in the hippocampus.

Topics: Animals; Depression; Electric Stimulation; Electroacupuncture; Exploratory Behavior; Galanin; Hippocampus; Hypertension; Male; Neurokinin A; Neuropeptide Y; Neuropeptides; Physical Exertion; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Substance P; Vasoactive Intestinal Peptide

The purpose of this study was to determine whether vasoactive intestinal peptide (VIP) elicits vasodilation in the in situ peripheral microcirculation of hamsters with spontaneous hypertension and whether encapsulation of VIP into liposomes modulates this response. Using intravital microscopy, we found that suffusion of VIP (0.05 and 0.1 nmol) alone over cheek pouch resistance arterioles of normotensive hamsters elicited significant vasodilation that was potentiated and prolonged by encapsulation of the peptide into liposomes (P < 0.05). By contrast, VIP (0.5 and 0.1 nmol) had no significant effects on arteriolar diameter in hamsters with spontaneous hypertension. However, encapsulation of VIP into liposomes restored its vasorelaxant effects in hypertensive animals, although the duration of vasodilation was significantly shorter in comparison with controls (P < 0.05). Empty liposomes had no significant effects on arteriolar diameter in either group. These data indicate that VIP-induced vasodilation in the peripheral microcirculation in situ is impaired in essential hypertension and that encapsulation of VIP into liposomes restores, in part, this response.

Topics: Acetylcholine; Animals; Arterioles; Capsules; Cricetinae; Drug Carriers; Hypertension; Liposomes; Male; Nitroglycerin; Vasoactive Intestinal Peptide; Vasodilation; Vasodilator Agents

Embryonic hypothalamic tissue originating from spontaneously hypertensive rats (SHR) was implanted in young normotensive Wistar Kyoto rats in an attempt to localize hypothalamic regions directly responsible for the induction of hypertension. A 25% increase in host systolic blood pressure as compared with the controls was recorded 3 months after implantation in the animals receiving rostral hypothalamic tissue (R-SHR), whereas blood pressure was not affected in the animals grafted with caudal hypothalamic tissue (C-SHR). The hypertension in the R-SHR group was accompanied by hypertrophy of the heart and kidneys. The number of vasopressin-immunopositive (VPi) parvocellular cells in the hypothalamic paraventricular nucleus (PVN) of the R-SHR group was massively reduced (by 72%), while that of the tyrosine hydroxylase-immunopositive cells displayed no change. In the suprachiasmatic nucleus of these animals the VPi cell number was unaltered. In the C-SHR, the amount of parvocellular VPi cells was also unaltered. Likewise, oxytocin-containing cells were the same in all groups. DNA nick-end labeling of the tissue revealed that PVN cells are undergoing programmed cell death. These results implicate a selective degeneration by hypothalamic PVN cells in the pathogenesis of hypertension.

Topics: Animals; Apoptosis; Brain Tissue Transplantation; Female; Fetal Tissue Transplantation; Hypertension; Hypertrophy; Hypothalamus; Immunoenzyme Techniques; Nerve Degeneration; Neurons; Pregnancy; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Tyrosine 3-Monooxygenase; Vasoactive Intestinal Peptide

The present report relates to pharmaceutical composition for the treatment of male impotence. The transdermal application of a potent derivative of vasoactive intestinal peptide (VIP) coupled to a suitable hydrophobic moiety (e.g. stearyl-VIP) in a suitable ointment composition (e.g. Sefsol) enhances sexual activity and erection formation in a variety of impotence models in rats (sterile rats, diabetic rats, and animals with high blood pressure). Furthermore, exchange of the methionine in position 17 with norleucine enhances biological activity. Thus, stearyl-Nle17-VIP may be considered useful for the treatment of impotence.

Topics: Administration, Cutaneous; Animals; Diabetes Mellitus, Experimental; Disease Models, Animal; Erectile Dysfunction; Hypertension; Kinetics; Male; Ointments; Orchiectomy; Penile Erection; Penis; Rats; Reflex; Skin; Tissue Distribution; Vasoactive Intestinal Peptide

Vasoactive intestinal peptide (VIP) has been localized within the suprachiasmatic nucleus of the hypothalamus (SCN) and appears to play an important role in the entrainment of circadian rhythms with the light-dark (LD) cycle. The spontaneously hypertensive rat (SHR), an inbred strain used extensively in research on primary hypertension, has significantly more VIP mRNA in its brain than normotensive Wistar-Kyoto control (WKY) rats. Because VIP levels are abnormally high in SHR rats the present study examined whether the mechanisms controlling circadian rhythms are also altered in SHR rats. When entrained to a 24 h LD cycle, SHR rats began their wheel-running rhythm approximately 1.5 h earlier than WKY controls. SHR rats re-entrained to a phase delay in the LD cycle more slowly than did WKY rats, but tended to re-entrain to a phase advance more rapidly. The free-running period of SHR rats in both constant light and constant dark was significantly shorter than that of WKY rats. In SHR rats, phase delays produced by 1-h pulses of light were less than one-half the magnitude of the delays seen in WKY rats; however, the phase advances were nearly twice that of WKY rats. Using in situ hybridization, the SCN levels of mRNA encoding VIP were found to be significantly greater in SHR rats, but the mRNA levels of another peptide important for entrainment, gastrin releasing peptide, did not differ between SHR and WKY rats. These data indicate that the mechanisms controlling circadian rhythms in SHR rats differ significantly from those controlling rhythms in WKY rats and that VIP mRNA is significantly elevated within the SCN of SHR rats. The role of VIP in the entrainment of circadian rhythms is discussed.

Topics: Animals; Autoradiography; Blood Pressure; Circadian Rhythm; Drinking; Hypertension; In Situ Hybridization; Male; Motor Activity; Rats; Rats, Inbred SHR; Rats, Inbred WKY; RNA, Messenger; Suprachiasmatic Nucleus; Vasoactive Intestinal Peptide

In order to study alterations of peripheral substance P (SP) and vasoactive intestinal peptide (VIP) in the immunoreactive nervous system in essential hypertension, plasma SP and VIP concentrations in stroke-prone spontaneously hypertensive rats (SHRSP) at 8, 12, 18, 28, 30, 35 and 48 weeks of age and age-matched Wistar-Kyoto rats (WKY) were measured, using enzyme immunoassays (EIAs). The mean plasma SP concentrations of SHRSP (n = 61) and WKY (n = 58) were 4.9 +/- 1.2 fmol/ml and 6.6 +/- 1.9 fmol/ml, respectively. The value of SHRSP was significantly lower than that of WKY (p < 0.01). The mean SP concentration of young SHRSP was significantly higher than those of other ages. The mean plasma VIP concentrations of SHRSP (n = 61) and WKY (n = 58) were 0.80 +/- 0.25 fmol/ml and 1.01 +/- 0.32 fmol/ml, respectively. The value of SHRSP was significantly lower than that of WKY (p < 0.01). These decreases in plasma SP and VIP concentrations of SHRSP were observed at all ages. Decreases in the peripheral release of SP and VIP from the endings of SP- and VIP-immunoreactive nerves of SHRSP were seen, and the functional involution of peripheral SP- and VIP-immunoreactive nerves in essential hypertension was suggested.

Topics: Animals; Cerebrovascular Disorders; Hypertension; Immunoenzyme Techniques; Male; Peripheral Nerves; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Substance P; Vasoactive Intestinal Peptide

Vasoactive intestinal peptide (VIP) was injected intravenously at a dose of 10 micrograms in spontaneously hypertensive and normotensive Wistar-Kyoto rats. In order to evaluate the hemodynamic and hormonal effects of this peptide, the mean arterial pressure, heart rate as well as a serum rLH and rPRL levels, the contents of LH-RH in hypothalamus and the content of LH in pituitary tissue were determined. The same procedure was applied in rats receiving placebo. Serum rPRL concentration was measured additionally after combined administration of VIP+dopamine. VIP injection produced a decrease in mean arterial pressure and an increase in heart rate in both spontaneously hypertensive and normotensive rats. Serum rPRL concentration was significantly increased at 10 minutes after injection. The combined therapy (VIP+dopamine) partially inhibited this response. Serum rLH concentration, the content of LH-RH in hypothalamic tissue as well as the content of pituitary LH after VIP injection in spontaneously hypertensive and normotensive rats did not differ from the values obtained for the control group.. 1. VIP injection produced the dramatic hypotensive effects in hypertensive rats; 2. A marked increase in PRL concentration in response to VIP was partially inhibited by dopamine in hypertensive and normotensive rats; 3. VIP injection did not change LH-RH and LH release in both hypertensive and normotensive rats.

Topics: Animals; Gonadotropin-Releasing Hormone; Hemodynamics; Hypertension; Hypothalamus; Luteinizing Hormone; Pituitary Gland; Prolactin; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Vasoactive Intestinal Peptide

Perivascular innervation in cerebral arteries of spontaneously hypertensive rats and of normotensive Wistar-Kyoto rats was studied. Adrenergic nerve fibers and neuropeptide Y-containing nerve fibers, indicative of vasoconstrictor nerves, were denser in all cerebral arteries of spontaneously hypertensive rats than those of Wistar-Kyoto rats. In contrast, cholinergic nerve fibers and vasoactive intestinal polypeptide, substance P-containing nerve fibers, indicative of vasodilator nerves, remained unchanged in all cerebral arteries of spontaneously hypertensive rats, as compared with findings in the Wistar-Kyoto rats. Thus, not only adrenergic nerve fibers but also neuropeptide Y-containing nerve fibers may play an important role in preventing the disruption of the blood-brain barrier and the development of hypertensive encephalopathy in spontaneously hypertensive rats.

Topics: Adrenergic Fibers; Animals; Brain Diseases; Cerebral Arteries; Cholinergic Fibers; Hypertension; Immunohistochemistry; Male; Neuropeptide Y; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Substance P; Vasoactive Intestinal Peptide; Vasoconstriction; Vasodilation

The role of the hypothalamus (HTH) in the pathogenesis of genetic hypertension was studied in spontaneously hypertensive rats (SHR). It is currently believed that, in this strain, the genetic defect manifests itself mainly in the HTH. We examined this hypothesis by grafting HTH neurons from embryos of SHR or control Wistar Kyoto (WKY) rats into the HTH of adult normotensive WKY rats. Changes in host systolic blood pressure (SBP) were monitored, and alterations in vasoactive intestinal polypeptide (VIP) gene expression of the host brain were studied. In rats grafted with HTH tissue from SHR embryos (G-SHR), the blood pressure rose by 31% as compared with that in the grafted control group. The blood pressure climbed gradually over a period of 6 weeks to its highest level, which was maintained for at least 3 months following grafting. Along with the elevated blood pressure, the heart weight increased by 80% compared to controls. Behavioral changes were also evident in the G-SHR rats, and these were similar to those of the native SHR strain. In situ hybridization histochemistry showed a 40% elevation in VIP transcripts in the suprachiasmatic nucleus of the host G-SHR brain compared to controls. These studies demonstrate that transplantation of embryonic SHR HTH tissue into brains of adult normotensive rats results in the development of hypertensive characteristics in the host. It thus appears that the HTH is a prime candidate for the source of changes leading to spontaneous hypertension in mammals.

Topics: Animals; Blood Pressure; Brain Tissue Transplantation; Fetal Tissue Transplantation; Hypertension; Hypothalamus; Immunohistochemistry; Myocardium; Neurons; Nucleic Acid Hybridization; Organ Size; Rats; Rats, Inbred SHR; Rats, Inbred WKY; RNA, Messenger; Vasoactive Intestinal Peptide; Vasopressins

The effects of endothelin, a novel potent vasoconstrictor peptide, on isolated portal veins were examined in spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Endothelin contarcted the portal vein from SHR and WKY, in a concentration-dependent manner. However, both twitch contraction and tonic contraction of portal veins in response to endothelin were significantly enhanced in SHR. In contrast to the effects of endothelin, twitch contractile responses to Bay K 8644 were not significantly different between vessels from SHR and WKY. These results indicate that endothelin is a potent vasoconstrictor peptide in the portal vein, and that the increased sensitivity in SHR may be due to an increase in the activity of voltage-dependent Ca2+ channels which is modulated by endothelin, but not to an increase in the activity of voltage-dependent Ca2+ channels which can be stimulated by Bay K 8644.

Topics: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; Animals; Calcium Channels; Endothelins; Hypertension; In Vitro Techniques; Isometric Contraction; Male; Mice; Muscle Contraction; Muscle, Smooth, Vascular; Peptides; Portal Vein; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Vasoactive Intestinal Peptide

Little is known about perivascular neuropeptides in hypertension in man. In this study we investigated the circulating levels of calcitonin gene-related peptide (CGRP)-, substance P- and vasoactive intestinal peptide-like immunoreactivity in 30 patients with severe hypertension before and after treatment for high blood pressure. Circulating levels of CGRP- and substance P-like immunoreactivity in the hypertensives were significantly different from the corresponding levels in 31 age- and sex-matched normotensive subjects. After normalization of blood pressure the mean levels of CGRP- and substance P-like immunoreactivity did not differ between the two groups. The levels of vasoactive intestinal peptide-like immunoreactivity remained unchanged. These observations suggest that vascular afferent nerves play a part in the maintenance of hypertension.

Topics: Adult; Aged; Antihypertensive Agents; Calcitonin Gene-Related Peptide; Drug Therapy, Combination; Female; Humans; Hypertension; Male; Middle Aged; Neuropeptides; Substance P; Vasoactive Intestinal Peptide; Vasodilation

Vasoactive intestinal peptide (VIP) is a potent vasodilator. We therefore set out to investigate VIP-gene expression in spontaneous hypertensive rats. By quantitative in situ hybridization histochemistry as well as by RNA blot hybridization experiments we discovered a significant increase in VIP transcripts in the brains of those hypertensive rats. We suggest that the increase in VIP-gene expression may play a compensatory role in these rats where otherwise the rise in blood pressure may have had a much more adverse effect.

Topics: Animals; Brain; Gene Expression Regulation; Hypertension; Nucleic Acid Hybridization; Rats; Rats, Inbred SHR; Rats, Inbred Strains; RNA, Messenger; Vasoactive Intestinal Peptide

The distribution and density of nerves containing vasoactive intestinal polypeptide, substance P, and neuropeptide Y around the cerebral and peripheral blood vessels of stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY) were studied using an indirect immunofluorescence technique. Neonatal sympathectomy of SHRSP with anti-nerve growth factor and guanethidine was also carried out to study the effect of sympathectomy on the distribution of these nerves. Vasoactive intestinal polypeptide nerve density was higher in the veins and superior mesenteric artery of SHRSP than of WKY and lower in the cerebral arteries of SHRSP than of WKY, but no difference was found in the muscular mesenteric arteries. Sympathectomy reduced the density of these nerves in all the peripheral vessels but had little effect on the cerebral arteries. Density of substance P nerves was similar between SHRSP and WKY in the peripheral vessels but higher in the cerebral arteries of WKY than of SHRSP. Sympathectomy reduced the density of these nerves in the peripheral vessels but increased the density in some cerebral arteries of SHRSP. Neuropeptide Y nerve density was higher in the peripheral blood vessels of SHRSP than of WKY, and no difference was found in the cerebral arteries. Sympathectomy almost completely removed these nerves in the peripheral vessels but had no effect on the cerebral arteries. We suggest that some of the differences in nerve density between SHRSP and WKY, especially those in the peripheral blood vessels, may be related to the development of hypertension in the SHRSP.

Topics: Animals; Blood Vessels; Cerebral Arteries; Hypertension; Male; Mesenteric Arteries; Neuropeptide Y; Neuropeptides; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Rats, Inbred WKY; Substance P; Vasoactive Intestinal Peptide

The regional brain and spinal cord concentrations of vasoactive intestinal polypeptide immunoreactivity (VIP) were measured in age-matched normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats. The relative order of distribution of VIP in the WKY strain was cortex (44 pmol/g) greater than hippocampus = striatum greater than midbrain = hypothalamus greater than medulla oblongata/pons = lumbar spinal cord (SC) greater than cervical SC greater than thoracic SC (2.5 pmol/g) whereas in the SH strain this order was cortex (35 pmol/g) greater than striatum = midbrain greater than hippocampus = hypothalamus greater than medulla oblongata/pons = lumbar SC greater than cervical SC greater than thoracic SC (1 pmol/g). The VIP concentrations of the thalamus, cerebellum and pituitary were at the level of assay sensitivity (0.5 pmol/g) in both strains. In comparison to the WKY, the SH rats had significantly lower VIP levels in the hippocampus (-42%) and cervical (-46%) and thoracic (-56%) spinal cord but significantly higher levels in the midbrain (+64%).

Topics: Animals; Central Nervous System; Female; Hypertension; Radioimmunoassay; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Vasoactive Intestinal Peptide

Amelioration or cure of hypertension, hypercortisolism, diarrhea with steatorrhea, and massive proteinuria resulted from excision of a pheochromocytoma that contained immunoreactive ACTH, VIP, and somatostatin. Ectopic ACTH production by the tumor was clearly the cause of the hypercortisolism, and the possible involvement of VIP and somatostatin in the diarrhea and steatorrhea was considered. The response to tumor removal suggested that the mesangioproliferative glomerulonephritis shown on renal biopsy was also a paraneoplastic phenomenon.

Topics: Adrenal Gland Neoplasms; Adrenocortical Hyperfunction; Adrenocorticotropic Hormone; Celiac Disease; Diarrhea; Humans; Hydrocortisone; Hypertension; Male; Middle Aged; Pheochromocytoma; Proteinuria; Somatostatin; Vasoactive Intestinal Peptide

Hypersecretion of catecholamine primarily affecting adrenaline levels arose in a patient given a jejunoileal bypass for severe obesity. Apart from organic factors, including a hetero and/or orthotopic pheochromocytoma and the therapeutic effect of beta-blocking drugs, it is suggested that the pathogenesis of the patient's condition is based on a hypersecretion of VIP, as sometimes occurs in patients with short intestine/syndrome.

Topics: Adult; Catecholamines; Epinephrine; Humans; Hypertension; Jejunoileal Bypass; Male; Norepinephrine; Obesity; Pheochromocytoma; Starvation; Vasoactive Intestinal Peptide

Topics: Animals; Crohn Disease; Gastrointestinal Diseases; Gastrointestinal Hormones; Hepatic Encephalopathy; Humans; Hypertension; Rats; Receptors, Cell Surface; Vasoactive Intestinal Peptide

A 2-year-old boy with failure to thrive, watery diarrhea, abdominal distention, hypokalemia, metabolic acidosis, and episodes of hypertension and sweating was found to have a calcified right lower quadrant mass. Blood levels of vasoactive intestinal peptide (VIP) and norepinephrine (NE) were elevated. Presurgical management with phenoxybenzamine hydrochloride and metyrosine was associated with an absence of expected postoperative hypotension, and resection of a benign ganglioneuroma resulted in prompt relief of all symptoms and return to normal of VIP and NE levels. Evidence supports the theory that VIP is the substance responsible for the diarrhea that accompanies some neural crest tumors.

Topics: Abdominal Neoplasms; Child; Child, Preschool; Female; Ganglioneuroma; Gastrointestinal Hormones; Humans; Hypertension; Infant; Male; Phenoxybenzamine; Tomography, X-Ray Computed; Tyrosine 3-Monooxygenase; Vasoactive Intestinal Peptide

Cardiac adenylate cyclase activity was normal in 3 weeks-old spontaneously hypertensive rats of the Wistar-Okamoto substrain. The hormone-sensitive adenylate cyclase activity was reduced in 10 weeks-old or older animals, and secretin- and VIP-activations were definitely more impaired (by 64% and 69%, respectively) than isoproterenol- and glucagon-activations (17% and 22%, respectively). By contrast, the fluoride- and p[NH]ppG-stimulations of the enzyme were unaffected. These alterations in the adenylate cyclase system coupled to secretin and VIP appeared specific to the heart as the isolated pancreatic acinar cells from spontaneously hypertensive animals responded normally to secretin, as a liver particulate fraction responded normally to secretin and VIP, and both brain synaptic membranes and a particulate fraction of anterior pituitary to VIP.

Topics: Adenylyl Cyclases; Aging; Animals; Brain; Enzyme Activation; Gastrointestinal Hormones; Glucagon; Hypertension; In Vitro Techniques; Isoproterenol; Liver; Male; Myocardium; Pancreas; Pituitary Gland, Anterior; Rats; Secretin; Vasoactive Intestinal Peptide

Topics: Catecholamines; Humans; Hypertension; Neuroblastoma; Paraganglioma, Extra-Adrenal; Pheochromocytoma; Prostaglandins; Vasoactive Intestinal Peptide