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)

In this pilot study we investigated the effects of a 4-h infusion of atrial natriuretic peptide (8-33 Met ANP) on hemodynamic, renal, and hormonal parameters in 12 patients with hypertension. Either 8-33 ANP in 5% mannitol (0.7 microgram/min [eight patients] and 1.05 micrograms/min [four patients]) or placebo (5% mannitol) was infused for 4 h on 2 consecutive days in a randomized double-blind crossover design. The plasma levels of ANP were not significantly different between the two doses of ANP and therefore the results from the two doses were combined. Plasma ANP increased from 61 +/- 24 pg/mL to 291 +/- 55 pg/mL after 2 h and to 288 +/- 40 pg/mL after 4 h. ANP caused a significant lowering of systolic blood pressure after 2 h of infusion from 148 +/- 5 mm Hg to 142 +/- 5 mm Hg (P less than .05) and to 128 +/- 6 after 4 h (P less than .01). Two hours after discontinuation of the infusion, systolic blood pressure was 126 +/- 6 and 135 +/- 7 mm Hg 4 h after the end of the infusion. Diastolic blood pressure did not change. Heart rate increased from 69 +/- 3 beats/min to 74 +/- 3 beats/min after 4 h and to 78 +/- 4 beats/min 2 h after termination of the infusion. Cardiac output did not change significantly. Urinary sodium and chloride increased significantly but creatinine clearance did not change. Plasma aldosterone decreased after 2 h of ANP infusion from 9.8 +/- 1.7 ng/dL to 6.7 +/- 0.9 ng/dL (P less than .01) and to 6.5 +/- 1.2 ng/dL after 4 h (P less than .05). Plasma renin activity decreased from 0.81 +/- 0.1 ng angiotensin I/mL/h to 0.57 +/- 0.1 after 2 h of infusion (P less than .05). There were no significant changes in plasma catecholamines or arginine vasopressin. Two patients developed severe hypotension and bradycardia and one of them had a sinus pause of 7.4 sec associated with loss of consciousness. Neither of these two patients had a significant increase in plasma catecholamines in response to the severe hypotension, suggesting that ANP may have inhibited their sympathetic response and increased their sensitivity to vagal cardioinhibitory reflexes. In conclusion, infusion of ANP in hypertensive patients causes prolonged lowering of systolic blood pressure with no change in diastolic pressure and cardiac output.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of atrial natriuretic peptide (8-33-Met ANP) in patients with hypertension. 153 72

Angiotensin II (Ang II) has been shown to induce proliferation of cardiac myocytes. To examine the role of Ang II in left ventricular (LV) hypertrophy, isoproterenol was infused subcutaneously into 9-week-old male Wistar rats at 4.2 mg/kg/day for 7 days. Infusion of isoproterenol increased LV weight and Ang II concentrations in plasma and in LV tissue. In anephric rats, LV weight and tissue Ang II were increased similarly, but plasma Ang II was not changed by isoproterenol. Concomitant oral administration of trandolapril and isoproterenol prevented increases in both LV Ang II and LV weight. Treatment with hydralazine decreased blood pressure in a similar way as trandolapril but did not affect either LV weight or LV Ang II. Plasma Ang II was not decreased by either trandolapril or hydralazine when administered in combination with isoproterenol. These results suggest that cardiac tissue Ang II regulates myocyte growth in isoproterenol-induced LV hypertrophy, and the reduction of Ang II partly explains the prevention of cardiac hypertrophy by the converting enzyme inhibitor.
Hypertension 1992 Jun
PMID:Role of cardiac angiotensin II in isoproterenol-induced left ventricular hypertrophy. 153 15

This article reports on the binding and the angiotensin II (Ang II) antagonistic properties of a peptide, referred to as hIIA, encoded by an RNA strand complementary to the human Ang II messenger RNA. Although Ang II and hIIA (H2N-Glu-Gly-Val-Tyr-Val-His-Pro-Val-COOH) share four amino acids, the iodinated and tritiated forms of hIIA were unreactive with seven monoclonal antibodies defining four distinct epitopes on the Ang II molecule and failed to bind to Ang II hepatic and mesangial receptors. However, hIIA did inhibit binding of 125I-Ang II to rat hepatocyte membranes (IC50, 2 x 10(-7) M) and to the various monoclonal antibodies. The lowest IC50 (5 x 10(-7) M) was measured with the monoclonal antibody specific for the Ang II sequence generally considered as implicated in receptor recognition. As predicted from the binding studies, hIIA was further shown to antagonize some biological properties of Ang II. On mesangial cells, hIIA alone had no effect on intracellular calcium concentration ([Ca2+]i) and prostaglandin E2 synthesis but did abolish the transient increase in [Ca2+]i in response to 100 nM Ang II and did induce a specific dose-dependent inhibition of the Ang II-stimulated prostaglandin E2 release. Furthermore, intravenous infusion of hIIA (200 micrograms.kg-1.min-1) inhibited by 66 +/- 3% the rat hypertensive response to 100 ng.kg-1 Ang II but had no effect on the pressor activity of agents such as alpha 1-adrenergic and HT2 serotonin agonists. Our data suggest that the "complementary" peptide hIIA interacts directly with Ang II by mimicking the Ang II complementary site on the receptor and can inhibit the physiological effects of Ang II. This type of Ang II complementary peptide may serve as a model for a new class of antihypertensive drugs.
Hypertension 1992 Apr
PMID:Antagonist effect of a receptor-mimicking peptide encoded by human angiotensin II complementary RNA. 155 66

Angiotensin II (Ang II) has been proposed to be an endogenous neuromodulator of the baroreceptor reflex at the level of the brain stem solitary-vagal area. Elevated activity of the brain Ang II system has been implicated in the development and maintenance of hypertension in spontaneously hypertensive rats and deoxycorticosterone acetate-salt hypertensive rats. In the present study, we sought to determine if Ang II receptors in the solitary-vagal area exhibited altered binding kinetics in spontaneously hypertensive rats or deoxycorticosterone-salt hypertensive rats. Ang II receptors were examined by quantitative autoradiographic analysis of iodine-125-labeled [Sar1,Ile8]Ang II binding in the solitary-vagal area in six groups of animals: 1) spontaneously hypertensive rats, 2) normotensive Wistar-Kyoto rats, 3) uninephrectomized rats, 4) uninephrectomized rats with a 1% solution of saline for drinking water, 5) uninephrectomized and deoxycorticosterone-treated rats, and 6) uninephrectomized and deoxycorticosterone-treated rats given a 1% solution of saline for drinking water. Blood pressure was significantly elevated in the spontaneously hypertensive rats and deoxycorticosterone-salt rats relative to control animals. There was a significant decrease in the binding affinity (increased KD) for 125I-[Sar1,Ile8]Ang II and a significant increase in the maximum binding density for 125I-[Sar1,Ile8]Ang II in the solitary-vagal area of spontaneously hypertensive rats relative to Wistar-Kyoto rats. Deoxycorticosterone-salt rats also exhibited significantly higher KD and maximum binding density values compared with controls. These results indicate that Ang II receptor binding is altered in the solitary-vagal area of two different models of experimental hypertension and suggest that these changes could contribute to the expression of the hypertensive state.
Hypertension 1992 Apr
PMID:Angiotensin II receptors in the solitary-vagal area of hypertensive rats. 155 67

The role of an increase in total peripheral resistance (TPR) and the contribution of angiotensin II (ANG II) to the hypertension induced by reduced uterine perfusion pressure (RUPP) was explored in pregnant rabbits. On the 22nd day of gestation, a catheter and a microthermocouple were placed in the aorta to measure mean arterial pressure (MAP) and cardiac output (CO), respectively. Three days later, RUPP was induced by a clip on the aorta proximal to the ovarian and distal to the renal arteries. Mean arterial pressure distal to the clip (uterine perfusion pressure) was reduced to 56 +/- 8% (mean +/- SD) of the initial level. Twenty-four hours later, MAP rose from 65 +/- 3 to 84 +/- 11 mm Hg; CO index decreased from 207 +/- 18 to 169 +/- 27 ml/min/kg; and TPR index increased from 0.32 +/- 0.03 to 0.51 +/- 0.08 mm Hg kg/ml/min, respectively (n = 7, all p less than 0.01). Sham-operated pregnant rabbits (n = 7) and non-P rabbits (n = 5) with a comparable distal aortic pressure reduction experienced no change in MAP or CO. Infusion of a receptor antagonist of angiotensin II (Sar1,Ile8-Ang II, 1 microgram/kg/min for 20 min) decreased MAP in sham-operated pregnant rabbits from 64 +/- 6 to 54 +/- 6 mm Hg (p less than 0.01) but did not change MAP in RUPP hypertensive rabbits (86 +/- 9 mm Hg before and 87 +/- 8 at the end of infusion, n = 6). These data indicate that RUPP in pregnant rabbits leads to a high resistance form of hypertension in which the formation of Ang II is not increased.
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PMID:Increased peripheral resistance during reduced uterine perfusion pressure hypertension in pregnant rabbits. 156 40

We tested the hypothesis that increased systemic vascular resistance in spontaneously hypertensive rats may be secondary to enhanced phospholipase C activity in response to vasoconstrictor stimuli. Activation of phospholipase C by angiotensin II (Ang II), thromboxane A2, arginine vasopressin, and endothelin-1 was compared in cultured glomerular mesangial cells and mesenteric vascular smooth muscle cells taken from 13- to 14-week-old hypertensive and normotensive Wistar-Kyoto rats (blood pressure, 185 +/- 1 versus 135 +/- 2 mm Hg). Phospholipase C was assessed by measuring cytosolic free calcium and by the accumulation of radiolabeled inositol phosphates. Basal cytosolic calcium did not differ between mesangial cells taken from both strains but was greater in smooth muscle cells from hypertensive rats (210.1 +/- 8.2 versus 149.2 +/- 4.7 nM). The responsiveness of cytosolic calcium and inositol phosphate accumulation to Ang II was significantly enhanced in mesangial cells from hypertensive rats (10(-7) M Ang II: peak increase of calcium, 1,266 +/- 181 versus 603 +/- 93 nM; percent increment of inositol phosphates at 1 minute, 266 +/- 26 versus 98 +/- 10%). Vascular smooth muscle cells from hypertensive rats, when compared with normotensive rats, showed a similar augmentation of Ang II-stimulated intracellular calcium and inositol phosphates. Thromboxane A2-induced enhancement of intracellular calcium and inositol phosphate accumulation in vascular smooth muscle cells was also greater in hypertensive animals. However, the responses to vasopressin and endothelin in mesangial or vascular smooth muscle cells did not differ between the normotensive and hypertensive animals. There was no significant difference in Ang II receptor number and affinity between hypertensive- and normotensive-derived mesangial cells. We conclude that genetically increased blood pressure in rats may be secondary to enhanced post-receptor signaling in glomerular mesangial cells activated by Ang II and to enhanced signaling in vascular smooth muscle cells stimulated by either Ang II or thromboxane A2.
Hypertension 1992 May
PMID:Phospholipase C responses in cells from spontaneously hypertensive rats. 156 63

Angiotensin II (Ang II)-mediated hypertension induces vascular smooth muscle cell hypertrophy and hyperplasia in systemic blood vessels, but the effects of Ang II on the intrinsic cell populations within the kidney have been less well characterized. We infused Ang II for 14 days into rats by minipump at doses (200 ng/min) that resulted in moderate hypertension (mean systolic blood pressure 156-172 mm Hg). Small renal arterial vessels of Ang II-infused rats demonstrated focal injury with fibrinoid necrosis and medial hyperplasia, whereas the glomerular capillaries demonstrated only rare segmental hyalinosis. Proliferation of vascular smooth muscle cells was pronounced (fourfold to 20-fold increase in [3H]thymidine incorporation) as opposed to a minimal proliferation of glomerular cells in Ang II-infused rats. In contrast, the principal effect of Ang II in glomeruli was to increase the expression of alpha-smooth muscle actin by mesangial cells and desmin by visceral glomerular epithelial cells. Ang II-infused rats also developed focal tubulointerstitial injury, with tubular atrophy and dilation, cast formation, an interstitial monocytic infiltrate, and mild interstitial fibrosis with increased type IV collagen deposition. The injury was associated with a proliferation of distal tubule, collecting duct, and interstitial cells as determined by immunostaining for proliferating cell nuclear antigen, and was accompanied by an increase in platelet-derived growth factor B-chain messenger RNA in the area of interstitial injury as localized by in situ hybridization. Renal interstitial cells also underwent phenotypic modulation in which they expressed alpha-smooth muscle actin. Vehicle-infused control rats displayed no tubular injury, proliferation, or phenotypic modulation. Thus, Ang II in doses that cause moderate hypertension induces marked vascular, glomerular, and tubulointerstitial injury with cell proliferation, leukocyte recruitment, phenotypic modulation with the upregulation of proteins normally associated with smooth muscle cells, and interstitial fibrosis.
Hypertension 1992 May
PMID:Renal injury from angiotensin II-mediated hypertension. 156 65

Hypertrophy of vascular smooth muscle cells (VSMC) is a pathogenic feature of hypertension which may contribute to abnormal vessel tone and function. As a consequence of the increase in cell size associated with hypertrophy, it is likely that alterations in the mechanisms that regulate VSMC intracellular volume occur. Because the Na+/H+ exchanger plays an important role in volume regulation and because we previously observed long term alterations in Na+/H+ exchange and pHi in response to angiotensin-II-induced (ang II) hypertrophy, we studied cell-acidifying mechanisms. To do this, we measured alkaline recovery from NH4Cl-mediated alkalinization, using the fluorescent dye, 2',7'-bis-(2-carboxyethyl)-5(6)-carboxyfluorescein. VSMC were growth-arrested (0.4% calf serum for 24 h) or hypertrophied (100 nM ang II in 0.4% calf serum for 24 h). Ang II-treated cells exhibited a 107% increase in alkaline recovery over control cells (13.86 +/- 1.87 versus 6.68 +/- 1.01 mmol H+/min/liter cells). The increase in alkaline recovery was not a result of increased Cl-/HCO-3 exchange becaue it was not HCO-3 dependent nor inhibited by 4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid. Studies with bumetanide and the sterically inhibited substrate N(CH3)4+ showed that the alkaline recovery was mediated by NH4+ transport via the Na/K/2Cl cotransporter. Ang II-treated cells exhibited a 334% increase in bumetanide-sensitive alkaline recovery over control cells (9.16 +/- 1.90 versus 2.11 +/- 1.46 mmol H+/min/liter cells). Ang II-treated cells also exhibited a 90% increase in bumetanide-sensitive 86Rb uptake over control cells. These findings demonstrate that Na/K/2Cl cotransport activity is specifically induced in ang II-hypertrophied VSMC and establish this transporter as a component of the hypertrophic growth response.
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PMID:The Na/K/2Cl cotransporter is increased in hypertrophied vascular smooth muscle cells. 156 72

A universal underlying abnormality in the pathogenesis of hypertension, atherosclerosis, myocardial dysfunction, and diabetic glomerulosclerosis involves alteration in smooth muscle cell structure, function, and growth. Angiotensin II, through its effects on contractility, growth, and the sympathetic nervous system, may potentially play a key role in this pathologic process and, thus, contribute to the development of these cardiovascular and renal complications of diabetes mellitus. Angiotensin-converting enzyme inhibitors and some direct renin inhibitors prevent or slow the progression of some of these complications, which further suggests a pathologic role for the reninangiotensin system in diabetes mellitus.
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PMID:Effect of the renin-angiotensin system in the vascular disease of type II diabetes mellitus. 158 Feb 75

Angiotensin II plays an important role in the kidney by regulating renal flow, glomerular filtration rate, mesangial cell function, and sodium reabsorption. Blockade of the renin-angiotensin system has powerful effects on kidney function. Studies in animal models of renal failure suggest that converting enzyme inhibitors slow down the inevitable progression of the renal failure. This could be in part due to their effect on reducing glomerular pressure or by reducing glomerular hypertrophy. In patients with malignant hypertension, diabetic nephropathy, and other causes of renal failure, preliminary evidence suggests that lowering the blood pressure with angiotensin-converting enzyme (ACE) inhibitors may possibly carry some other benefits compared with other blood pressure lowering regimens. However, single drug therapy is rarely sufficient to control blood pressure in these patients. Further properly controlled randomized trials should give a clear indication of whether any particular class of drug has any advantage in slowing down the progressive renal impairment for a given lowering of blood pressure. In patients with renovascular hypertension ACE inhibitors are effective drugs in lowering blood pressure. However, in certain settings they may cause a reversible decline in renal function.
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PMID:Blood pressure, angiotensin-converting enzyme (ACE) inhibitors, and the kidney. 158 Feb 76


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