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)

1. Dibutyryl cyclic AMP (Db cAMP, 75-500 microgram/kg), injected into the lateral ventricle of the brain of the cat increased blood pressure, heart rate and splanchnic discharge rate. 2. ATP, but not AMP, induced similar changes; GMP in small doses increased blood pressure. 3. A number of drugs are known to activate adenylate cyclase-induced hypertension, tachycardia and increase splanchnic discharge rate. This was shown for TRH, tetracosactide and a new beta2-adrenoceptor stimulant, NAB 365. 4. Injection into the lateral ventricle of theophylline or Ro 7/2956, both inhibitors of phosphodiesterase, similarly increased blood pressure. 5. Histamine administered by the same route induced similar reactions; it is not known if this action was exerted by activation of H1- or H2-receptors. 6. Somatostatin, known to reduce cAMP levels, induced a small but significant decrease in blood pressure. Melanocyte stimulating hormone release inhibiting factor (MIF) and TSH were ineffective. 7. These results provide evidence for the possibility of a role for cAMP in the central regulation of blood pressure at suprabulbar levels.
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PMID:Cyclic 3'5'-adenosine monophosphate and central circulatory control in cats and dogs. 2 Feb 56

The present study investigated the role of arachidonic acid and acetylcholine in mediating endothelium-dependent relaxations of rabbit aorta. Isolated thoracic aortic rings were precontracted with a submaximal concentration of norepinephrine, and the effect of various agents on arachidonic acid- and acetylcholine-induced relaxations was examined. Arachidonic acid elicited a concentration-related relaxation that was potentiated by the cyclooxygenase inhibitor indomethacin. Treatment with the lipoxygenase inhibitor nordihydroguaiaretic acid completely blocked but the cytochrome P450 inhibitor metyrapone had no effect on arachidonic acid-induced relaxation. NG-Monomethyl-L-arginine and nitro-L-arginine, compounds that inhibit the nitric oxide-like endothelium-derived relaxing factor, had little or no effect on arachidonic acid-induced relaxations. In contrast, nordihydroguaiaretic acid, metyrapone, NG-monomethyl-L-arginine, and nitro-L-arginine all attenuated the relaxation to acetylcholine; however, indomethacin had no effect on acetylcholine-induced relaxations. Arachidonic acid and acetylcholine had no effect on denuded rabbit aorta. Incubation of rabbit aorta with [14C]arachidonic acid resulted in the synthesis of major radioactive metabolites that comigrated with the prostaglandins and hydroxyeicosatetraenoic acids. Indomethacin selectively inhibited prostaglandin formation, nordihydroguaiaretic acid attenuated both prostaglandins and hydroxyeicosatetraenoic acids, and metyrapone blocked the epoxyeicosatrienoic acids. Additionally, acetylcholine elicited a twofold increase in tissue cyclic guanosine monophosphate content in contrast to a 59% reduction in cyclic guanosine monophosphate content observed with arachidonic acid. Therefore, these data suggest that in rabbit aorta, arachidonic acid-induced relaxations are mediated by an endothelium-dependent factor (or factors) that differs from the factor (or factors) released by acetylcholine. These results support the existence of multiple endothelium-derived relaxing factors.
Hypertension 1992 Nov
PMID:Arachidonic acid- and acetylcholine-induced relaxations of rabbit aorta. 133 Sep 23

At least two types of receptors for natriuretic peptides have been reported: biologically active receptors coupled with guanylate cyclase (atrial natriuretic peptide [ANP]-B receptors) and clearance receptors (ANP-C receptors). To elucidate the role of protein kinase C (PKC) in the regulation of ANP-B receptors, vascular smooth muscle cells in culture were treated with phorbol ester. Incubation with receptor agonists and phorbol ester led to the desensitization of receptor-mediated cyclic guanosine monophosphate (ANP-B receptor response) in rat vascular smooth muscle cells. Although a PKC inhibitor and downregulation of PKC by long-term incubation of cells with phorbol esters blocked the phorbol ester-induced desensitization of the ANP-B receptor response, they did not block the ANP-induced desensitization of the ANP-B receptor response. In addition, when desensitization by phorbol esters was observed, ANP was still capable of desensitization. These observations suggest that the mechanism for regulating ANP-B receptor sensitivity may be both PKC-dependent and PKC-independent and mediated by phorbol esters and ANP, respectively.
Hypertension 1992 Apr
PMID:Phorbol ester and atrial natriuretic peptide receptor response on vascular smooth muscle. 134 39

Nitric oxide (NO) and atrial natriuretic factor (ANF) cause vascular relaxation by generating cyclic guanosine monophosphate (cGMP) via activation of the soluble and particulate guanylate cyclases, respectively. The chronic effects of NG-nitro-L-arginine methyl ester (L-NAME), an L-arginine antagonist and NO synthase inhibitor, on the blood pressure and plasma and aortic cGMP levels of rats were tested. Wistar rats (n = 10 per group) were given doses of L-NAME (0, 1, 5, 10, 20, 50, and 100 mg/kg.d) by gavage twice a day for 4 wk. Chronic L-NAME induced a time- and dose-dependent increase in blood pressure. The total heart weight/body weight ratio did not change in any group, despite the hypertension. The plasma levels of cGMP did not change significantly in any group, and were correlated with the plasma ANF levels (r = 0.51, P less than 0.0001). Aortic cGMP decreased in negative correlation with increasing L-NAME from 0 to 10 mg/kg.d, culminating in a 10-fold drop arterial wall cGMP. The aortic cGMP content of rats in the four highest dose groups (from 10 to 100 mg/d) tended to increase slightly and was positively correlated with endogenous ANF (r = 0.48, P less than 0.002, n = 40). Intravenous L-arginine decreased arterial blood pressure and reversed the decline in aortic cGMP. Exogenous ANF and sodium nitroprusside both significantly increased aortic cGMP. Neither the arterial wall concentrations of cGMP-dependent kinase nor cAMP was changed by L-NAME. Thus, chronic blockade of NO synthase with L-NAME induces a dose-dependent increase in blood pressure and decrease in aortic cGMP. The in vivo basal aortic cGMP seems to be mainly dependent on NO synthase: soluble guanylate cyclase activity and to a minor extent on particulate guanylate cyclase activity.
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PMID:Determinants of aortic cyclic guanosine monophosphate in hypertension induced by chronic inhibition of nitric oxide synthase. 137 15

Cicletanine (CIC), a furopyridine derivative, lowers blood pressure in hypertensive animals and humans. We have previously identified an NaCl-sensitive substrain of spontaneously hypertensive rat (SHR-S) that displays enhanced sensitivity to the depressor effects of exogenous atrial natriuretic peptide (ANP) when fed a high NaCl diet. The current study tested the hypotheses that CIC has an exaggerated antihypertensive effect in NaCl-supplemented SHR-S and that this effect might be ANP dependent. CIC (40 mg/kg/day) or vehicle was administered by gavage in a single daily dose for three weeks beginning immediately prior to initiation of 1% or 8% NaCl diets in seven-week-old male SHR-S. CIC significantly decreased mean arterial pressure (MAP) and the ratio of left ventricular and septum weight to body weight (LV + S/BW) in both 8% NaCl- and 1% NaCl-fed SHR-S. The depressor effect of CIC was greater in the 8% NaCl group (-26 mmHg) than in the 1% NaCl group (-13 mmHg). CIC was associated with significant reduction in RAP in the 8% NaCl group but not in the 1% NaCl group. Neither CIC treatment nor 8% NaCl significantly altered plasma ANP or cyclic guanosine monophosphate (GMP) levels in plasma, aorta, or kidney. CIC was associated with significant decreases in plasma norepinephrine (NE) levels in the 1% NaCl group but not in the 8% NaCl group. The data demonstrate that the antihypertensive effect of CIC is exaggerated in NaCl-sensitive hypertension. The antihypertensive effect of CIC appears not to be related to ANP or cyclic GMP but may be related to a combination of a sympatholytic and natriuretic/diuretic effects in SHR-S.
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PMID:Antihypertensive effect of cicletanine is exaggerated in NaCl-sensitive hypertension. 164 1

It has been suggested that the impaired natriuretic response of the clipped kidney in two-kidney, one clip hypertensive rats is related to downregulation of renal atrial natriuretic peptide receptors. To test this hypothesis, blood volume expansion and atrial peptide binding studies were performed in this model. Infusion of 1% and then 1.5% body weight donor blood (n = 6) caused a progressive increase in plasma immunoreactive atrial natriuretic peptide (107 +/- 26 to 168 +/- 31 to 427 +/- 154 pg/ml, p less than 0.001); the sodium excretion of the nonclipped kidney rose from 230 to 2,200 to 4,000 neq/min (p less than 0.01) but that of the clipped kidney did not rise significantly. There was a highly significant correlation between log cyclic guanosine monophosphate and log sodium excretion by the nonclipped (r2 = 0.749) but not the clipped (r2 = 0.046) kidney. Between clipped and nonclipped kidneys, the association constant (5.26 +/- 0.89 versus 5.17 +/- 0.64 x 10(9)/mol) and apparent binding site density (575 +/- 92 versus 500 +/- 74 fmol/mg protein) for atrial peptide binding in isolated glomeruli did not differ. Assay of atrial peptide-induced cyclic guanosine monophosphate release by isolated glomeruli showed that clipped and nonclipped kidneys were equally responsive. Binding affinity and receptor density did not differ in homogenates prepared from inner medullas of clipped and nonclipped kidneys. These results show that the blunted natriuretic response in clipped kidneys was not associated with any relative decrease in number or function of glomerular or papillary atrial natriuretic peptide receptors.
Hypertension 1991 Oct
PMID:Renal atrial peptide receptors and natriuresis in two-kidney, one clip hypertension. 165 51

The vasodilator potency of human atrial natriuretic factor-(99-126) was investigated in the forearm vascular bed of 10 young and 10 elderly normotensive volunteers with venous occlusion strain gauge plethysmography. Atrial natriuretic factor was infused at six increasing dose steps into the brachial artery from 0.001 up to 0.3 microgram/min/100 ml of forearm volume. This induced a mean +/- SEM increase in blood flow from 1.4 +/- 0.2 up to 6.0 +/- 1.0 ml/min/100 ml in the young and from 1.4 +/- 0.2 up to 3.9 +/- 0.6 ml/min/100 ml in the elderly. The dose-response curves of forearm blood flow and of forearm vascular resistance after increasing infusion rates of atrial natriuretic factor were shifted to the right in the elderly when compared with the young subjects. The mean percent decrease in forearm vascular resistance, induced by atrial natriuretic factor, during this dose-response curve averaged -31 +/- 3% in the elderly versus -56 +/- 3% in the young subjects (p = 0.0002). The calculated forearm spillover of the second messenger of atrial natriuretic factor, cyclic guanosine monophosphate, significantly increased from baseline values of 1.2 +/- 1.1 and 0.7 +/- 0.5 pmol/min/100 ml in young and elderly subjects, respectively, up to 23.2 +/- 5.0 and 30.5 +/- 7.0 pmol/min/100 ml during the highest dose of atrial natriuretic factor (both p less than 0.01 versus baseline). There were no significant differences in the increments of the forearm spillover of this second messenger between both age groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1991 Nov
PMID:Attenuated forearm vasodilator response to atrial natriuretic factor in the elderly. 165 70

The aim of this prospective study was to investigate both vasoconstricting and vasodilating plasma hormones and plasma factors regulating the circulatory homeostasis in patients with endstage congestive heart failure before and early after orthotopic heart transplantation and to evaluate factors which may influence their regulation. 19 patients with endstage congestive heart failure were analyzed serially before and 3-4 weeks after orthotopic heart transplantation. A significant decrease in plasma concentrations of noradrenaline (457 +/- 202 vs. 204 +/- 88 pg/ml; p less than 0.001), adrenaline (43 +/- 32 vs. 26 +/- 11 pg/ml), atrial natriuretic peptide (341 +/- 218 vs. 139 +/- 64 pg/ml; p less than 0.005), cyclic guanosine monophosphate (13.8 +/- 7.8 vs. 6.6 +/- 2.2 pmol/ml, p less than 0.05) and in plasma renin activity (16.6 +/- 13.0 vs. 2.0 +/- 2.4 ng AI/ml/h; p less than 0.01) was found after transplantation. The data indicate that the marked increase in plasma catecholamine concentrations and renin activity in endstage congestive heart failure is reversible as early as 3-4 weeks after heart transplantation. This is most likely the consequence of normalization of cardiac function. While elevation of atrial natriuretic peptide and cyclic guanosine monophosphate as well as increased vasoconstrictor activity in heart failure appear to be related to impaired ventricular function, the persistent moderate elevation of both vasodilating agents after transplantation may be compensatory to counteract cyclosporin-induced arterial hypertension after heart transplantation.
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PMID:Plasma hormones in patients with chronic heart failure before and early after orthotopic heart transplantation. 166 Oct 55

The arterial vasodilator properties of the calcium antagonist diltiazem were investigated by measurement of changes of forearm blood flow during brachial artery infusions of eight dosages of diltiazem in eight hypertensive patients. Forearm blood flow increased and calculated forearm vascular resistance decreased dose-dependently (maximum decrease of 83.5 +/- 8.6%). When comparing the effects of calcium influx inhibition by diltiazem with stimulation of the vascular cyclic guanosine monophosphate (GMP) system by sodium nitroprusside, the vasodilation by diltiazem was approximately 1.6 times greater, attesting to its potent arterial vasodilator activity. The clinical efficacy and feasibility of diltiazem monotherapy was evaluated in 40 patients with mild to moderate essential hypertension treated with a slow-release formulation of diltiazem, 90 mg twice daily over 8 weeks, and in a subgroup of 21 patients with two tablets of 90 mg once daily in the morning over a period of 2 weeks. Blood pressure was lowered significantly and to a similar extent by either twice- or once-daily administration of diltiazem. This effect was maintained during open long-term therapy over a mean of 11 months. Heart rate and body weight did not change. Thus, the vasodilator properties of diltiazem can be utilized for effective long-term treatment of hypertension. The possibility of once-daily dosing may prove useful with respect to drug compliance in the long-term treatment of a generally asymptomatic disease such as hypertension.
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PMID:Arterial vasodilator and antihypertensive effects of diltiazem. 170 18

Endothelial cells contain an enzyme(s) which produces nitric oxide from L-arginine in response to a variety of mechanical stimuli as well as to autacoids and local and circulating hormones. Nitric oxide is a potent vasodilator and inhibitor of platelet function; it exerts its effects via activation of soluble guanylate cyclase and subsequent formation of cyclic 3'-5'-guanosine monophosphate. In the kidney, activation of the endothelial L-arginine pathway is associated with increases in renal blood flow, diuresis and natriuresis, while the glomerular filtration rate remains constant. The activity of the endothelial L-arginine pathway is impaired in hypertension and during chronic therapy with cyclosporine A. In addition, diabetes and atherosclerosis impair this pathway. Thus, the endothelial L-arginine pathway plays an important role in the local regulation of blood flow. Alterations in the activity of this pathway may play an important role in the pathophysiology of hypertension and renal disease.
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PMID:The endothelial L-arginine/nitric oxide pathway and the renal circulation. 175 83


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