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

Nitric oxide (NO) has been identified as a naturally-occurring metabolite in mammalian systems, formed from the amino acid arginine in response to a variety of physiological stimuli. It appears to function in cell-cell communication and may act either directly or through the stimulation of cyclic GMP synthesis in the regulation of such diverse functions as smooth muscle relaxation, inhibition of platelet aggregation and adhesion, central nervous system activity, and cytostasis. The significant role(s) could have important biomedical implications since perturbations in the biosynthesis, release or actions of NO could lead to hypertension, CNS dysfunction or increased susceptibility to infection. Understanding the enzymology and regulation of this pathway in various tissues may lead to development of pharmacological agents specifically designed for the rational control of nitric oxide formation and action.
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PMID:Nitric oxide. New discoveries, biomedical implications. 202 96

To investigate whether altered renal medullary prostaglandin (PG) synthesis is involved in the development of hypertension in spontaneously hypertensive rats (SHR), we compared the hormonal responsiveness of cultured renal papillary collecting tubule (RPCT) cells from SHR and Wistar-Kyoto rats (WKY) as control. Basal levels of PGE2 and cAMP were lower in 4-weeks-old SHR than in WKY, while PGE2 synthesis after stimulation with arachidonate, A23187 or bradykinin and the level of cAMP responded to vasopressin or exogenous PGE2 were similar in both strains. There was no difference in basal nor stimulated levels of cGMP between both strains. In 16-week-old rats, basal levels of cAMP, cGMP and PGE2 were significantly lower than in 4-week-old rats, but no differences were recognized between both strains. These results suggest that RPCT cells of SHR and WKY at the post-weaning period may differ in the metabolism of PGE2 and cAMP. This difference may be attributed to the possible defect in arachidonate availability in SHR.
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PMID:[Responsiveness of cultured papillary collecting tubules to vasoactive hormones: comparison between spontaneously hypertensive rats and Wistar-Kyoto rats]. 206 16

Atrial natriuretic factor (ANF) is degraded by neutral endopeptidase. We hypothesized that neutral endopeptidase inhibition (NEP-I) increases sodium excretion and that this effect would be potentiated in the presence of an isolated increase in intrarenal ANF. In seven anesthetized dogs, ANF was infused into one renal artery to produce pathophysiologic concentrations in the supplemented kidney while the control kidney received physiologic circulating concentrations of ANF. In the control kidney, NEP-I (SQ 28,603) produced significant increases in urine flow, absolute sodium excretion and fractional sodium excretion while glomerular filtration rate (GFR) remained constant. These renal actions of NEP-I were associated with marked increases in urinary excretion of ANF and cyclic GMP consistent with decreased renal degradation and increased biologic activity of ANF. All of these effects were significantly greater in the supplemented kidney. The present study suggests that NEP-I produces natriuresis which appears to be independent of changes in GFR. In addition, while NEP-I mimics the renal action of pathophysiologic levels of ANF, NEP-I also potentiates the natriuretic effects of pathophysiologic concentrations of ANF as observed in congestive heart failure or hypertension.
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PMID:Neutral endopeptidase inhibition potentiates the renal actions of atrial natriuretic factor. 214 48

Two subclasses of cyclic guanosine monophosphate (GMP)-specific phosphodiesterases were identified in vascular tissue from several beds. The activity of one subclass (phosphodiesterase IB) was stimulated severalfold by calmodulin and selectively inhibited by the phosphodiesterase inhibitor TCV-3B. The activity of the other subclass (phosphodiesterase IC) was not stimulated by calmodulin and was selectively inhibited by the phosphodiesterase inhibitor M&B 22,948. To assess the involvement of both subclasses in regulating cyclic GMP-dependent responses, the ability of TCV-3B and M&B 22,948 to potentiate the in vitro and in vivo responses to the endogenous guanylate cyclase stimulator atrial natriuretic factor (ANF) was evaluated. Both TCV-3B and M&B 22,948 relaxed isolated rabbit aortic and pulmonary artery rings and also potentiated the relaxant effect of ANF. In addition, both inhibitors produced small increases in urine flow and sodium excretion in anesthetized rats and potentiated the diuretic and natriuretic responses to exogenous ANF. M&B 22,948 (30 micrograms/kg/min) produced a threefold increase in the natriuretic response to simultaneously administered ANF, and TCV-3B (10 micrograms/kg/min) produced a twofold increase in the response to ANF. The results of the present experiments suggest that both the calmodulin-sensitive and calmodulin-insensitive subclasses of cyclic GMP-specific phosphodiesterase play a role in regulating the in vitro and in vivo response to ANF.
Hypertension 1990 May
PMID:Subclasses of cyclic GMP-specific phosphodiesterase and their role in regulating the effects of atrial natriuretic factor. 215 39

The great discovery by Furchgott of the relaxing factor released from the endothelium (EDRF) awakened us to the necessity to reevaluate the functional importance of endothelial cells that have been chemically or physically stimulated. EDRF was first demonstrated to be released by acetylcholine, substance P, bradykinin and calcium ionophore A23187; thereafter, many substances have been found to release EDRF. This factor is quite unstable, is not produced by cyclooxygenase, and is an activator of soluble guanylate cyclase that synthesizes cyclic GMP; its action is suppressed by antioxidants via the superoxide anions produced, potentiated by superoxide dismutase and abolished by methylene blue and oxyhemoglobin. Recently, the role of lipoxygenase products in the production of EDRF was evaluated with new 5-lipoxygenase inhibitors without antioxidant activity. During the last couple of years, the actions and chemical properties of EDRF were verified to be quite similar to those of nitric oxide (NO); therefore, the hypothesis of "EDRF = NO" is widely being accepted. NO is produced from L-arginine via catalysis by an enzyme that is activated by Ca2+. The enzyme activity is inhibited by L-monomethyl arginine and other L-arginine analogs. Chemical and physical stimulations increase intracellular Ca2+ in endothelial cells that seems to be associated with K(+)-channel opening and hyperpolarization. Current interests are directed to the possible roles of NO in the regulation of nerve function. There are evidences suggesting that NO modulates adrenergic nerve function in blood vessels and some brain cell functions regulated by cellular cyclic GMP. Particularly, NO may be a transmitter substance in non-adrenergic, non-cholinergic vasodilator nerves innervating the cerebral arteries. Future investigations will determine the physiological roles of EDRF or NO and its relationships to pathophysiology of vascular dysfunctions, such as vasospasm and those related to hypertension, diabetes, aging, etc., and the extended roles of NO in nerve function, inflammation, immune reactions, etc. would be clarified more extensively by accelerated progress in this field of research.
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PMID:[Endothelium-derived relaxing factor (EDRF)]. 216 93

By using the differential diagnosis of traditional Chinese medicine to determine the types of hypertension, using the diagnosis of western medicine (WM) to determine the phases of hypertension, 61 inpatients of Liver Yang exuberance type hypertension were randomly divided into Qigong group and WM group. The patients in the Qigong group were treated with both Qigong and antihypertensive drugs at low dosage, but those in the WM group were treated with the drugs alone. Several laboratory tests concerning sympathetico-adrenomedullary functions were conducted twice respectively at 1st and 9th week after hospitalization of the patients. The results indicated that the Qigong group after treatment of 9 weeks had more cases with normal sympathetico-adrenomedullary functions than it had before the treatment, and that their urinary CA, E, NE decreased, MHPG-SO4 increased, plasma cAMP and cGMP got down, but cAMP/cGMP ratio got up. It suggested that Qigong could modulate the sympathetico-adrenomedullary functions of patients with Liver Yang exuberance type hypertension.
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PMID:[Effect of qigong on sympathetico-adrenomedullary function in patients with liver yang exuberance hypertension]. 216 14

Vascular remodeling is central to the pathophysiology of hypertension and atherosclerosis. Recent evidence suggests that vasoconstrictive substances, such as angiotensin II (AII), may function as a vascular smooth muscle growth promoting substance. To explore the role of the counterregulatory hormone, atrial natriuretic polypeptide (ANP) in this process, we examined the effect of ANP (alpha-rat ANP [1-28]) on the growth characteristics of cultured rat aortic smooth muscle (RASM) cells. ANP (10(-7) M) significantly suppressed the proliferative effect of 1% and 5% serum as measured by 3H-thymidine incorporation and cell number, confirming ANP as an antimitogenic factor. In quiescent RASM cells, ANP (10(-7), 10(-6) M) significantly suppressed the basal incorporations of 3H-uridine and leucine by 50 and 30%, respectively. ANP (10(-7), 10(-6) M) also suppressed AII-induced RNA and protein syntheses (by 30-40%) with the concomitant reduction of the cell size. Furthermore, ANP also significantly attenuated the increase of 3H-uridine and leucine incorporations caused by transforming growth factor-beta (4 x 10(-11), 4 x 10(-10) M), a potent hypertrophic factor. These results indicate that ANP possesses an antihypertrophic action on vascular smooth muscle cells. Down-regulation of protein kinase C by 24-h treatment with phorbol 12,13-dibutyrate did not inhibit ANP-induced suppression on 3H-uridine incorporation. Based on the observation that ANP was more potent than a ring-deleted analogue of ANP on inhibiting 3H-uridine incorporation, we conclude that the ANP's inhibitory effect is primarily mediated via the activation of a guanylate cyclase-linked ANP receptor(s). Indeed 8-bromo cGMP mimicked the antihypertrophic action of ANP. Accordingly, we speculate that in addition to its vasorelaxant and natriuretic effects, the antihypertrophic action of ANP observed in the present study may serve as an additional compensatory mechanism of ANP in hypertension.
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PMID:Atrial natriuretic polypeptide inhibits hypertrophy of vascular smooth muscle cells. 217 26

Atrial natriuretic peptide (ANP) is secreted by the heart in response mainly to atrial distension and circulates in plasma in picomolar concentrations. It binds to receptors in blood vessels which it relaxes, renal glomeruli where it induces increased glomerular filtration rate, renal papilla to produce natriuresis, adrenal glomerulosa cells to inhibit aldosterone secretion, and median eminence and pituitary where it may inhibit vasopressin secretion. In experimental models of hypertension plasma levels of ANP are uniformly elevated, except in spontaneously hypertensive rats, in which plasma ANP may only rise transiently. The action of ANP on smooth muscle cells of the blood vessel wall results in production of cyclic GMP, which appears to be the second messenger producing relaxation of pre-contracted blood vessels. Mechanisms other than cGMP generation have been proposed but remain unproven as mediators of ANP action. Receptors for ANP in blood vessels are of two subtypes: B-receptors (or R1-receptors), which contain guanylate cyclase in their structure, and C-receptors (or R2-receptors), which have not been shown to the present to be biologically active. Our studies on vascular ANP receptors are reviewed. In several experimental models of hypertension such as saralasin-insensitive 2-kidney, 1-clip and 1-kidney, 1-clip Goldblatt hypertensive rats and in DOCA-salt hypertensive rats, we have found elevated plasma ANP, as well as decreased binding and ANP-induced vascular relaxation and blood pressure-lowering effects of ANP. Both the B and C ANP receptors appear decreased in density, even after acid washing of membranes to remove any retained circulating ANP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vascular receptors for atrial natriuretic peptide in hypertension. 217 36

An increased platelet-vessel wall interaction plays an important role in most forms of cardiovascular disease. In healthy arteries, the vascular endothelium prevents platelet adhesion and aggregation. As a mediator of this protective function, the endothelium produces prostacyclin, endothelium-derived nitric oxide and tissue plasminogen activator. Cardiovascular risk factors such as hypertension, hyperlipidemia and diabetes are associated with an increased platelet activation and with decreased antithrombotic properties of the blood vessel wall. The available inhibitors of platelet function interfere only with one of various mechanisms of platelet activation and of the platelet-vessel wall interaction. Prostaglandin inhibitors, such as aspirin and newer, more specific inhibitors, prevent the production and/or the effect of thromboxane A2 on platelets and the blood vessel wall. Other drugs interfere with the effect of adenosine diphosphate on platelets, or they increase intracellular concentration of cyclic GMP or AMP in platelets and vascular smooth muscle cells. The protective effects of platelet inhibitors in primary and particularly in secondary prevention of cardiovascular diseases have been documented in numerous studies. The successful clinical use of these substances, however, requires a selective prescription of the drugs in patients with cardiovascular disease.
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PMID:[Thrombocyte inhibitors in cardiovascular therapy]. 221 49

Pinacidil is a novel, clinically effective vasodilator used for the treatment of hypertension whose mechanism of action has not been precisely defined. In vitro, pinacidil (ED50 = 0.3 microM) was approximately 30-fold less potent than nitroglycerin and 700-fold more potent than minoxidil or hydralazine in relaxing rat aortic strip preparations. Aortic relaxations produced by nitroglycerin and acetylcholine were dramatically antagonized by methylene blue (10(-5) M), an inhibitor of soluble guanylate cyclase. In contrast, relaxation to hydralazine or minoxidil was unaffected and relaxation to pinacidil was only modestly inhibited (approximately threefold) by methylene blue (10(-5) M). Furthermore, aortic relaxation to pinacidil was similar in preparations with and without an intact endothelium. Relaxation induced by pinacidil (10(-7)-10(-4) M) was not associated with any elevation in either cyclic AMP (cAMP) or cyclic GMP (cGMP) levels in vitro, although nitroglycerin (10(-6) M) but not minoxidil (10(-3) M) or hydralazine (10(-3) M) significantly elevated cGMP levels. Thus, pinacidil was a potent relaxant agonist in vitro, in contrast to minoxidil and hydralazine, which were considerably weaker in this regard. Vascular relaxation produced by pinacidil was independent of an intact endothelium and was not associated with elevations in either cAMP or cGMP. These data are consistent with the proposal that the antihypertensive activity of pinacidil is due to nonspecific arterial vasodilation.
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PMID:Effects of pinacidil on serotonin-induced contractions and cyclic nucleotide levels in isolated rat aortae: comparison with nitroglycerin, minoxidil, and hydralazine. 243 46


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