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)

A study was performed to investigate the neurohypophyseal dopaminergic axis in terms of its biosynthetic activity and possible changes associated with spontaneous hypertension (SHR). An in vitro system was used in which isolated neuro-intermediate lobes were incubated with the catecholamine precursor, 3H-tyrosine. Dopamine (DA) content and 3H-DA were monitored using electrochemical detection coupled with high pressure liquid chromatographic separation. A time course study showed that there was significant incorporation of 3H-tyrosine into 3H-DA. In the SHR, both neurohypophyseal DA content and biosynthetic activity were reduced. Tissue levels of 3H-DA decreased from 651 to 297 dpm/posterior pituitary. A test of the effect of dehydration on neurohypophyseal dopaminergic activity revealed that water deprivation (48 hrs) caused an increase in DA biosynthesis in the hypertensive, but not the normotensive animal. This may have been due to a greater stimulation of the neurohypophyseal axis in the SHR since these animals showed significantly higher plasma vasopressin levels and hematocrits in response to dehydration. These results demonstrate that the neurohypophysis contains an active dopaminergic system which is altered in genetic hypertension.
 ...
PMID:Neurohypophyseal dopamine biosynthesis in the spontaneously hypertensive rat. 733 97

The noradrenaline concentration and the alpha-methyl-para-tyrosine (alpha-MPT)-induced disappearance of noradrenaline were determined in several nuclei of the hypothalamus and the medulla oblongata of renal hypertensive rats (two-kidney Goldblatt hypertension). A decreased alpha-MPT-induced disappearance of noradrenaline was found in the nucleus interstitialis striae terminalis and the nucleus paraventricularis 3 days after renal artery constriction, when blood pressure was slightly, but significantly higher than that of sham operated rats. At this stage the alpha-MPT-induced disappearance of noradrenaline was enhanced in the nucleus commissuralis and the A1-region of hypertensive rats while the noradrenaline concentration in the A1-region was significantly elevated. No significant differences were found in both parameters in hypothalamic and medullary nuclei 3.5 weeks after the operation, when hypertension had fully developed. These findings are indicative of the occurrence of transient changes in the activity of noradrenergic neurons located in the medulla oblongata and projecting to the hypothalamus during the initiation of the development of two-kidney Goldblatt hypertension.
 ...
PMID:Noradrenaline concentration and turnover in nuclei of the hyothalamus and the medulla oblongata at two stages in the development of renal hypertension in the rat. 740 5

ACE inhibitors are superior to other vasodilators in the treatment of congestive heart failure and may be advantageous in patients with myocardial infarction and hypertension. The mechanisms mediating these beneficial effects are not clear. The present article discusses the mechanisms leading to augmented release of endothelium-derived nitric oxide during ACE inhibition. Acute potentiation of bradykinin (Bk)-induced vasodilation was studied in rings of bovine and human coronary arteries mounted in organ chambers for recording of isometric force. The ACE inhibitors captopril, enalaprilat, fosinoprilat, lisinopril, or ramiprilat alone did not affect vascular tone in isolated coronary tone in isolated coronary artery preparations with intact endothelium. However, in the presence of exogenous Bk, kallidin, or one of the slowly degradable Bk2-receptor agonists D-Arg(Hyp3)-Bk or [Hyp3-Tyr(Me)8]-Bk they elicited potent concentration-dependent relaxations. Relaxations in response to lisinopril were not observed in the presence of other vasodilators. They were prevented by mechanical removal of the endothelium, inhibition of nitric oxide synthase or Bk2-receptor blockade. The data indicate that ACE inhibitors potentiate the effects of Bk on endothelial cells by a local mechanism, probably independent of the degradation of bradykinin. The chronic effects of ACE inhibitors on endothelial function were compared with those of selective angiotensin(AT)1-receptor blockade in cyclosporin A (CsA) treated rats. Chronic AT blockade alone does not affect endothelium-dependent relaxation and increases contractions to ATII in the rot aorta. Combination of CsA with either an ACE-Inhibitor or an AT2 receptor antagonist prevented the endothelial dysfunction in the rat arta observed after CsA alone.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Endothelium-mediated vasodilation during ACE inhibition. 755 74

In three separate experiments, 4 to 5-week-old spontaneously hypertensive rats (SHR) and normotensive controls (Wistar-Kyoto [WKy]) were exposed to hypobaric hypoxia (simulated altitude = 3658 m) for 3 hr, 3 days, or 3 weeks. Comparable groups were maintained in ambient laboratory conditions (normoxia). Hypoxia prevented the increase in blood pressure noted in 8-week-old normoxic SHR. Right ventricular hypertrophy first occurred after 3 days of hypoxia, and was found in both SHR and WKy. Catecholamine turnover was measured using the tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine. In myocardium, both strains evidenced hypoxia-induced changes in norepinephrine (NE) turnover, which was increased at 3 hr, normalized at 3 days, and increased again at 3 weeks. Reduced basal NE concentration at 3 days indicated a temporary deficit in synthetic capacity, which would allow maintenance of a heightened neuronal output. Catecholamine turnover in right and left ventricles differed little in response to hypoxia, in spite of differential hemodynamic demands on SHR versus WKy or on right versus left ventricle. In contrast to findings in myocardium, significant interactive effects between strain and altitude exposure were noted for adrenal catecholamine turnover. Specifically, hypoxia exerted a suppressive influence in SHR that was not evident in WKy, and this may represent an important component of hypoxia-induced protection against the development of spontaneous hypertension.
 ...
PMID:Time-dependent changes in catecholamine turnover in spontaneously hypertensive rats exposed to hypoxia. 770 Aug 91

Increased activity of the sympathetic nervous system has been described in chronic renal failure, but its role in the genesis and maintenance of hypertension associated with this condition has not been established. The kidney has an intense network of chemoreceptors and baroreceptors that send impulses to the brain. To what extent activation of these receptors by the scarred kidney or the uremic milieu may contribute to this model of hypertension is unknown. In the present study, we evaluated the effect of bilateral dorsal rhizotomy on the development of hypertension and neuroadrenergic activity in the anterior, lateral, and posterior hypothalamic nuclei, in the locus ceruleus, and in the nucleus tractus solitarius of Sprague-Dawley rats that underwent 5/6 nephrectomy or were sham operated. Neuroadrenergic activity was determined by calculating norepinephrine turnover rate after inhibition of norepinephrine synthesis with alpha-methyl-DL-p-tyrosine methyl ester hydrochloride. The endogenous norepinephrine concentration was significantly greater in the posterior and lateral hypothalamic nuclei and the locus ceruleus, but not in the nucleus tractus solitarius, and the anterior hypothalamic nuclei of uremic rats compared with control rats. In rats with chronic renal failure and sham rhizotomy, the turnover rate of norepinephrine in the posterior (15.3 +/- 1.61 nmol.g-1.h-1) and lateral hypothalamic nuclei (11.7 +/- 2.12 nmol.g-1.h-1) and in the locus ceruleus (26.6 +/- 2.42 nmol.g-1.h-1) was significantly faster (P < .01) than in rats with renal failure and dorsal rhizotomy (4.1 +/- 0.51, 4.7 +/- 0.77, and 5.1 +/- 1.13 nmol.g-1.h-1, respectively) or control animals with or without rhizotomy.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1995 Apr
PMID:Renal afferent denervation prevents hypertension in rats with chronic renal failure. 772 47

11 beta-Hydroxysteroid dehydrogenase (11-HSD) catalyzes the interconversion of cortisol and cortisone. This activity is postulated to protect the type I (mineralocorticoid) receptor from excessive concentrations of cortisol, allowing aldosterone to function as a mineralocorticoid. An enzyme with 11-HSD activity was isolated from rat liver and the corresponding rat and human cDNA and genomic clones isolated. This enzyme is a member of the "short chain dehydrogenase" family. Using site-directed mutagenesis, it was demonstrated that two highly conserved residues, Tyr-179 and Lys-183, are required for enzymatic function. Elimination of the amino terminus or the two glycosylation sites also destroys enzymatic activity. This may be due to actual disruption of enzymatic function or to effects on intracellular localization or stability of the enzyme. Examination of patients with apparent mineralocorticoid excess, a syndrome of juvenile hypertension thought to represent 11-HSD deficiency, did not reveal any mutations in the gene for this enzyme. There is substantial evidence for a second 11-HSD isozyme with distinct kinetic properties that is expressed in the renal distal tubule and possibly other sites of mineralocorticoid action. Apparent mineralocorticoid excess may involve this enzyme.
 ...
PMID:Functional studies of 11 beta-hydroxysteroid dehydrogenase. 779 18

We have proposed that L-3,4-dihydroxyphenylalanine (L-DOPA) is a neurotransmitter and/or neuromodulator in the central nervous system [Misu Y. and Goshima Y. (1993) Trends pharmac. Sci. 14, 119-123]. This study aimed to explore whether or not endogenous L-DOPA, as a neurotransmitter candidate of the primary baroreceptor afferents, tonically functions to activate depressor neurons in the nucleus tractus solitarii of anesthetized rats. By parallel microdialysis in bilateral nucleus tractus solitarii areas, the basal L-DOPA release was in part inhibited by tetrodotoxin perfusion (1 microM) or Ca2+ deprivation, and was markedly reduced by alpha-methyl-p-tyrosine (200 mg/kg, i.p.), a tyrosine hydroxylase inhibitor. Forty to 100 mM K+ concentration-dependently released L-DOPA. Fifty millimoles K+ repetitively and constantly released L-DOPA. This release was Ca(2+)-dependent. Stimulation of the left aortic nerve (100 Hz, 8 V) repetitively and constantly released L-DOPA and this release was tetrodotoxin-sensitive. Phenylephrine i.v. infused produced L-DOPA release and reflex bradycardia, temporally associated with a rise and subsequent recovery of blood pressure. This release and bradycardia were abolished by denervation of the bilateral carotid sinus and aortic nerves. In addition, L-DOPA methyl ester, a competitive L-DOPA antagonist, when microinjected into depressor sites of the left nucleus tractus solitarii, antagonized depressor responses to mild stimulation (20 Hz, 3 V) of the ipsilateral aortic nerve. This antagonist alone, microinjected bilaterally, elicited a dose-dependent hypertension, which was abolished by alpha-methyl-p-tyrosine. Furthermore, by immunocytochemical analysis seven days after denervation of the left aortic nerve, tyrosine hydroxylase- and L-DOPA-, but not dopamine- and dopamine-beta-hydroxylase-immunoreactivities decreased in the ipsilateral nucleus tractus solitarii and dorsal motor vagus nucleus complex area. In the left ganglion nodosum, denervation decreased staining and number of L-DOPA-immunoreactive cells and staining of tyrosine hydroxylase-immunoreactive cells, but no modification of dopamine-immunoreactive cells was seen. Taken together with previous findings that L-DOPA itself is stereoselectively responsible for cardiovascular control in this nucleus, it is probable that L-DOPA is a neurotransmitter of the primary baroreceptor afferents terminating directly in depressor neurons and/or indirectly in some neurons within a microcircuit, including depressor neurons of the nucleus tractus solitarii. Endogenously released L-DOPA itself tonically functions to activate depressor neurons for regulation of blood pressure in the rat nucleus tractus solitarii.
 ...
PMID:Baroreceptor-aortic nerve-mediated release of endogenous L-3,4-dihydroxyphenylalanine and its tonic depressor function in the nucleus tractus solitarii of rats. 781 96

By microdialysis in the rostral ventrolateral medulla (RVLM) of anesthetized rats, the spontaneous L-3,4-dihydroxyphenylalanine (DOPA) release was partially Ca(2+)-dependent and tetrodotoxin-sensitive and was markedly reduced by alpha-methyl-p-tyrosine (alpha-MPT; 200 mg/kg, i.p.). K+ (50 mM) Ca(2+)-dependently evoked L-DOPA. By microinjections into unilateral RVLM, L-DOPA (30-300 ng) produced dose-dependent hypertension and tachycardia similarly in rats untreated, treated with i.p. 3-hydroxybenzylhydrazine, a central DOPA decarboxylase inhibitor, or with i.v.t. 6-hydroxydopamine. These responses were antagonized by L-DOPA methyl ester (1.5 micrograms), a competitive L-DOPA antagonist. D-DOPA, dopamine, noradrenaline or adrenaline (300 ng) produced no effect. Furthermore, L-DOPA methyl ester alone microinjected into bilateral RVLM (2 micrograms x 2) produced prolonged hypotension and bradycardia, which were abolished by alpha-MPT. These data suggest that L-DOPA is relevant to modulation of sympathetic activity in the rat RVLM.
 ...
PMID:Evidence for L-dopa relevant to modulation of sympathetic activity in the rostral ventrolateral medulla of rats. 790 2

Autonomic dysreflexic hypertension occurs in up to 80% of spinal cord injury patients with lesions thoracic level 6 or higher. Pharmacologic agents directed at each part of the autonomic dysreflexic circuit were tested for efficacy in a rat model. Guanethidine (15 mg/kg intraperitoneally), alpha-methyl-paratyrosine (20 mg/kg intraperitonally), propranolol (3 mg/kg intraperitonally) and control were each tested on groups of three rats with intrinsic control blood pressure measurements. Results show an increase of 15 +/- 5 mm Hg diastolic pressure in control animals compared with no detectable increase with guanethidine or alpha-methyl-paratyrosine. There was an 11 +/- 2 mm Hg increase in diastolic pressure with propranolol. In conclusion, screening drug trials show that the ganglionic blocking agent, guanethidine, and competitive tyrosine uptake precursor, alpha-methyl-paratyrosine, effectively blocked dysreflexic hypertension, whereas the beta-blocker, propranolol, did not.
 ...
PMID:Pharmacologic treatment of autonomic dysreflexia in the rat. 791 19

In an earlier study, we reported that chronic intravenous administration of the V1 agonist [Phe2,Ile3,Orn8]vasopressin (V1AG) results in sustained hypertension. The present study was designed to determine whether V1-induced hypertension may be related specifically to intrarenal actions of this peptide. Chronic infusion of the V1 agonist into the medullary interstitial space of a single remaining kidney of normal, conscious Sprague-Dawley rats at the rate of 2 ng.kg-1.min-1 for 14 days resulted in a sustained rise of 18 mmHg of mean arterial pressure (MAP). After withdrawal of V1AG, MAP returned to the baseline level. During the first day of V1AG infusion, there was a net loss of body sodium and no evidence of fluid retention throughout the period of hypertension. Plasma osmolality, sodium and potassium concentration, and water intake and body weight were not significantly affected by medullary interstitial infusion of V1AG. Renal medullary interstitial infusion of an equimolar amount of arginine vasopressin (AVP) did not affect MAP. Chronic medullary interstitial infusion of the selective V1 antagonist d(CH2)5[Tyr(Me)2,Ala-NH(2)9]AVP in equimolar amounts (2.5 ng.kg-1.min-1) prevented the MAP increase elicited by intravenous V1AG. However, intravenous administration of the V1 antagonist at the same rate together with V1AG (n = 7) failed to prevent hypertension. The results indicate that hypertension can be elicited by chronic stimulation of renal medullary V1 vasopressin receptors. They also suggest that some V2 agonistic properties of AVP may restrict the hypertensive action of this hormone. The mechanism for the rise of arterial pressure remains to be determined.
 ...
PMID:Prolonged stimulation of intrarenal V1 vasopressin receptors results in sustained hypertension. 797 48


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