Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The release of 5-hydroxytryptamine from the vascular adrenergic nerve by periarterial nerve stimulation in spontaneously hypertensive rats (SHR) was compared with that in normotensive Wistar-Kyoto rats (WKY). The isolated mesenteric vascular bed was perfused at a constant flow rate of 5 ml/min. Vasoconstrictor responses to periarterial nerve stimulation (4, 8, 12, and 16 Hz for 30 seconds) and 5-hydroxytryptamine (1 microM), but not norepinephrine (1 nmol), were significantly greater in SHR than in WKY. After treatment with 5-hydroxytryptamine (1 microM) for 15 minutes, vasoconstrictor responses to periarterial nerve stimulation previously reduced by prazosin (50 nM) were restored and a frequency-dependent pressor response reappeared. However, 5-HT treatment did not significantly affect the pressor response to exogenously administered norepinephrine (1 nmol), which was previously inhibited by prazosin. The degree of the restoration in SHR was significantly greater than that in WKY at all frequencies used. The restoration of the pressor response to periarterial nerve stimulation after 5-hydroxytryptamine treatment did not occur in the presence of the selective 5-hydroxytryptamine2 receptor antagonists ketanserin (10 nM) or LY53857 (10 nM). In the perfused mesenteric vascular bed of both WKY and SHR prelabeled with [3H]5-hydroxytryptamine, periarterial nerve stimulation (4-16 Hz) evoked a frequency-dependent increase in tritium efflux that was abolished by Ca2+-free Krebs-Ringer solution or tetrodotoxin (100 nM) and treatment with 6-hydroxydopamine. The tritium efflux evoked by periarterial nerve stimulation was significantly greater in SHR than in WKY at all frequencies used. These results suggest that the release of 5-hydroxytryptamine from adrenergic nerve endings by periarterial nerve stimulation is enhanced in the mesenteric vascular bed of the SHR.
Hypertension 1987 Sep
PMID:Enhanced 5-hydroxytryptamine release from vascular adrenergic nerves in spontaneously hypertensive rats. 362 84

The hemodynamic effects of p-chloroamphetamine (PCA), an indirect serotonin (5-HT) agonist, were studied in conscious, unrestrained rats. PCA caused an immediate hypotension and bradycardia followed by a dose-dependent increase in mean arterial pressure (MAP), which lasted for 15 to 60 min, associated with variable effects on heart rate. An intermediate dose increased MAP and resistance in hindquarter and mesenteric, but not renal, vascular beds. The pressor effect of PCA was blocked by prazosin and by 6-hydroxydopamine plus adrenal demedullation, but not by 6-hydroxydopamine or adrenal demedullation separately. Ganglionic blockade with chlorisondamine or beta adrenoceptor blockade with propranolol potentiated the pressor response to PCA, whereas several manipulations of central 5-HT systems (fluoxetine, methysergide and 5,7-dihydroxytryptamine) reduced but did not eliminate the hypertension observed after PCA. The initial bradycardia and hypotension were abolished by chlorisondamine or atropine but not reduced by any other pretreatment, whereas the variable heart rate response was converted to a marked, sustained tachycardia by ganglionic blockade or atropine and to a consistent bradycardia by propranolol and peripheral sympathectomy. The data suggest that PCA causes an immediate central or reflex vagal activation to decrease heart rate and MAP, followed by a central 5-HT-mediated increase in sympathetic activity that increases MAP. Most of the pressor effect observed between 5 and 30 min after PCA appears to be mediated by a direct effect on release of norepinephrine and epinephrine from sympathetic nerve terminals and the adrenal medulla, respectively. Only a minor part of the hemodynamic response to PCA appears to be attributable to its effect on release of 5-HT in the brain.
 ...
PMID:Hemodynamic pharmacology of p-chloroamphetamine, a serotonin agonist, in conscious rats. 368 94

Steady state levels of monoamine neurotransmitters were examined in SHR, a genetic model of hypertension and compared to its normotensive control (WKY). SHR and WKY were also challenged with alpha 2-adrenergic antagonists, (yohimbine, YOH, idazoxan) or an alpha 1-antagonist (prazosin) and alterations in CNS monoamine metabolism evaluated. SHR were found to have elevated levels of NE and 5-HT in a number of brain regions involved in cardiovascular control when compared to WKY. DA levels and metabolism were also altered in the SHR. Blockade of alpha 2-adrenoceptors and other direct and indirect actions of YOH exacerbated the abnormalities in central monoaminergic neurotransmission in SHR. Significant decreases in NE content were produced by YOH or idazoxan treatment in both SHR and WKY, presumably the result of the inhibition of alpha 2-adrenoceptor medicated presynaptic control of NE release. YOH treatment abolished the differences in steady state levels of NE between SHR and WKY, however, idazoxan did not. YOH administration resulted in significant increases in DA and 5-HT in a number of brain regions of both SHR and WKY. Idazoxan or prazosin produced few changes in DA and 5-HT metabolism except for increases in DA content in the spinal cord and brainstem of SHR given idazoxan. The YOH-induced increases in DA and 5-HT content of SHR were of a greater magnitude than the WKY in several brain regions. DOPAC levels were significantly elevated by YOH in both WKY and SHR, reflecting the antidopaminergic properties of YOH. 5-HIAA content was significantly reduced by YOH in a number of brain regions in both SHR and WKY, however, this effect was attenuated in several brain regions in SHR. The results of the present study demonstrate the multifarious nature of the alterations in CNS monoamine metabolism in SHR.
 ...
PMID:Yohimbine-induced alterations of monoamine metabolism in the spontaneously hypertensive rat of the Okamoto strain (SHR). II. The central nervous system (CNS). 369 Mar 64

Infusion of prostacyclin during cardiopulmonary bypass (CPB) reduces platelet activation, diminishes postoperative blood loss and decreases arterial blood pressure. In spite of continuous prostacyclin infusion, there is a delayed gradual rise in arterial pressure and resistance from low initial levels. We measured epinephrine (E), norepinephrine (NE), serotonin (5-HT), angiotensin II (ATII) and arginine-vasopressin (AVP) in plasma and carried out hemodynamic studies in 19 patients operated for coronary vascular disease. Eight patients served as a control group and were subjected to routine CPB. Eleven patients received prostacyclin 50 ng/kg/min during CPB. E and NE increased four- to sixfold during CPB from about 0.5 ng/ml (P less than 0.001). There was no difference between the groups. During CPB AVP increased sixfold from about 20 pg/ml in both groups (P less than 0.001), decreased early after CPB and increased again to high levels 3 h after CPB. The combined action of E, NE and AVP is of likely importance for the rise in systemic vascular resistance and/or need of vasodilation during CPB in the control group. ATII did not increase in the control group, but increased fourfold to about 20 pg/ml (P less than 0.01) during CPB in the prostacyclin group. The addition of AT II to E, NE and AVP seems responsible for the gradual return of arterial pressure and resistance during prostacyclin infusion. Postoperative hypertension and/or need of vasodilation 3 h after CPB was associated with high AVP levels in both groups. Hypotension caused by prostacyclin infusion did not increase E, NE or AVP above levels produced by CPB and moderate hypotension alone.
 ...
PMID:Effects of cardiopulmonary bypass and prostacyclin on plasma catecholamines, angiotensin II and arginine-vasopressin. 388 84

Using strains of spontaneously hypertensive rats with different degrees of hypertension, the influence of the duration of hypertension on platelets was examined through changes in platelet serotonin contents. The blood pressures of these strains were in the descending order of m-SHRSP greater than SHRSP greater than SHR greater than WKY. Serotonin content in normotensive WKY platelets was maintained in the range of 0.715 +/- 0.048(17) n mole/10(8) through ages 5-50 weeks in both sexes. In contrast with WKY of the same age and sex, a significant decrease in platelet serotonin content began to be observed in male m-SHRSP at 18-weeks of age, in female m-SHRSP and male SHRSP at 22-weeks of age, and in female SHRSP at 32-weeks of age, respectively. The content in SHR platelets of both sexes was unaltered up to 40-weeks of age. The time of the appearance of these exhausted platelets coincided with the reported time of scanning electron microscopic observation of vascular injuries in each strain of rats. It has been concluded that a long duration of hypertension causes platelets to become degranulated and exhausted due to in vivo activation of platelets at sites of arterial injury. Thus the changes of platelet contents could be an indicator of vascular injuries.
 ...
PMID:The appearance of exhausted platelets due to a duration of hypertension in stroke-prone spontaneously hypertensive rats. 398 98

Intrinsic vascular responsiveness to norepinephrine, transmural electrical stimulation, 5-hydroxy-tryptamine, and vasopressin was studied in isolated helical cut strips of cystic artery (downstream branch of hepatic artery) from 120 subjects and related to blood pressure. Blood pressure, thickness of the tunica media, and passive elastic properties of arterial strips were each significantly correlated with age. With the exception of blood pressure in the female subjects, it is doubtful that these relationships are of major biologic significance. Nevertheless, in subgroup formation, care was taken to control for age. Hypertension was arbitrarily defined in three different ways as: (a) two diastolic pressure measurements greater than or equal to 90 mm Hg (HT90); (b) two diastolic pressure measurements greater than or equal to 95 mm Hg (HT95); or (c) treatment for hypertension instituted by a physician 6 months to 2 years after arteries were studied (HTQ). In arteries of hypertensive female subjects, responsiveness to norepinephrine (and possibly to 5-hydroxytryptamine) was increased significantly over the first half of the dose-response curve, particularly in the arteries of HT95 and HTQ subjects. Responses to transmural electrical stimulation and vasopressin were not consistently different. Such differences were not seen in arteries of male subjects where, if anything, responsiveness to norepinephrine (but not 5-hydroxytryptamine) was decreased. The present observations were made in the absence of any substantive difference in arterial dimensions (e.g., cross-section area) or in the maximal response to norepinephrine. The data support the notion that, at least for female subjects, alteration in intrinsic vascular responsiveness may play a role in the pathogenesis of human essential hypertension.
 ...
PMID:Relationship of blood pressure to the responsiveness of an isolated human artery to selected agonists and to electrical stimulation. 608 64

The results in the group of III ventricle tumors, that is a decrease in the ventricular concentration of 5-HIAA in CSF, show that the hypothalamic metabolism of 5-HT is of importance for the concentration of 5-HIAA in the CSF. The results in posterior fossa tumors and in non communicating hydrocephalus (non tumor patients) for 5-HIAA and HVA confirm that the reabsorption of the metabolites from CSF occurs mainly in the caudal region of the ventricular system: the data in communicating hydrocephalus demonstrate that the intracranial hypertension can interfere by itself with the out transport mechanism of the metabolites from CSF. The results in normotensive idiopathic hydrocephalus sustain the hypothesis of a disturbance in 5-HT metabolism: it seems possible to separate this group from patients with secondary hydrocephalus in which the intracranial hypertension is only clinically compensated. The results in lumbar determinations demonstrate that in intracranial hypertension there is an impairment of the reabsorption of 5-HIAA also in the lumbar subarachnoid spaces. The concentration of 5-HIAA can depend mainly on the spinal cord metabolism, while lumbar HVA derives from the brain metabolism.
 ...
PMID:[Physiopathology of neurotransmitter metabolites in the cerebrospinal fluid in brain tumors]. 620 57

Serotonin injected in the left atrium activates a cardiogenic hypertensive chemoreflex in dogs. To elucidate patterns of the neural traffic, records were obtained from thoracic sympathetic efferent nerves (either the anterior ansa of the left stellate ganglion or the T4 input to the left stellate) in 8 anesthetized dogs with chest open. Serotonin (200 micrograms, left atrium) caused a massive sympathetic discharge during the hypertension and bracardia characteristic of the chemoreflex. Following the initial sympathetic discharge, there was a consistent post-excitatory depression of neural traffic, to a level significantly less than control discharge (two-tailed p less than .05). This post-excitatory depression began 11 +/- 5.4 (S.D.) seconds after injection of serotonin and 6.6 +/- 5.3 seconds after the peak neural discharge. It lasted 140 +/- 94 seconds, being maximal initially with gradual recovery. Complete block of the hypertension by the combined administration of phentolamine, propranolol, and nitroglycerin failed to abolish the efferent neural events, including post-excitatory depression, in all but one dog. We conclude that post-excitatory depression in thoracic sympathetic efferent neural traffic cannot be mediated exclusively through the secondary engagement of a baroreceptor mechanism and that it most likely is an integral part of the cardiogenic hypertensive chemoreflex.
 ...
PMID:Post-excitatory depression in thoracic sympathetic efferent neural traffic during a cardiogenic hypertensive chemoreflex. 629 55

Bradykinin (BK) produced concentration-related relaxations of cat middle cerebral arteries and was ineffective in cat basilar arteries. On rabbit basilar arteries, BK initially produced concentration-related relaxations; however, when repeated at 2-hour intervals, BK eventually produced pure contractile responses. After preincubation of the tissues with cycloheximide, BK produced reproducible relaxation responses. The angiotensin-converting enzyme inhibitors, SQ 14,225, BPP5a, and BPP9a, had no effect on the concentration-effect curves of BK, AII, or 5-HT with any of the preparations, but responses to AI were inhibited. These results suggest that, in these tissues, angiotensin-converting enzyme is important for conversion of AI to AII, but apparently not for the degradation of BK.
Hypertension
PMID:Angiotensin-converting enzyme, bradykinin, angiotensin, and cerebral vessel reactivity. 631 57

The serotonin (5-hydroxytryptamine, 5-HT) antagonist, ketanserin, has a high affinity for 5-HT2-receptors but it also binds to alpha 1-adrenoceptors. The compound (10 mg i.v.) lowered mean arterial pressure by 22% +/- 2% (mean +/- SEM, p less than 0.001) in 30 patients with essential hypertension. Measurements of heart rate, cardiac output, cardiac filling pressures, forearm blood flow, renal blood flow, and glomerular filtration rate revealed a hemodynamic pattern compatible with vasodilation of both resistance and capacitance vessels. This was accompanied by moderate reflex cardiostimulation. Ketanserin did not alter the pressor effect of bolus injections of (-)-phenylephrine hydrochloride (25, 50, 100, and 200 micrograms i.v.). Ketanserin also had a distinct hypotensive effect in four normotensive patients with autonomic insufficiency due to an efferent sympathetic lesion, who were unresponsive to phentolamine (20 mg i.v.). Thus, ketanserin in the dose we have used appears to lower blood pressure independently of alpha 1-adrenoceptor blockade. On the other hand, in patients with essential hypertension the antihypertensive effect of ketanserin was blunted by pretreatment with prazosin (12 mg/day). Therefore, a certain degree of alpha 1-adrenergic tone seems to be required for the compound to exert its full antihypertensive action. The findings are indirect evidence for a role of 5-HT in the maintenance of increased vascular resistance in essential hypertension. This may be related, at least in part, to the alleged amplifying effect of 5-HT on alpha 1-adrenoceptor-mediated vasoconstriction.
Hypertension
PMID:5-HT, alpha-adrenoceptors, and blood pressure. Effects of ketanserin in essential hypertension and autonomic insufficiency. 631 78


<< Previous 1 2 3 4 5 6 7 8 9 10