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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

This study examined effects of nonpeptide angiotensin II (Ang II) receptor subtype antagonists on the interaction of sympathetic function and Ang II in pithed rats. Effects of spinal cord stimulation (0.5-4 Hz) and norepinephrine (0.3-3 micrograms/kg i.v.) on mean arterial pressure (recorded with a carotid arterial catheter), cardiac output (measured with an electromagnetic flowmeter and flow probe around the thoracic ascending aorta), total peripheral resistance, and heart rate were determined. The subtype 1-selective Ang II receptor antagonist losartan (previously known as DuP 753) at 10 mg/kg i.v. blocked the hemodynamic responses to Ang II at 1 microgram/kg i.v. It inhibited mean arterial pressure and total peripheral resistance responses but not cardiac output and heart rate responses to spinal cord stimulation. In contrast, it reduced mean arterial pressure and cardiac output responses but not total peripheral resistance and heart rate responses to intravenous norepinephrine. Given at 100 mg/kg i.v., the subtype 2-selective receptor antagonist PD123177 did not reduce hemodynamic responses to intravenous Ang II, spinal cord stimulation, and intravenous norepinephrine. These results suggest that endogenous Ang II facilitates the release of norepinephrine from sympathetic nerve terminals in the vasculature of pithed rats. Similar to the Ang II receptor in vascular smooth muscle, the prejunctional Ang II receptor in pithed rats appears to be of subtype 1.
Hypertension 1992 Jun
PMID:Effect of blocking angiotensin II receptor subtype on rat sympathetic nerve function. 159 64

The effect of aging on the renin angiotensin system (RAS) was studied in 30 patients with renovascular hypertension and 33 patients with essential hypertension. Plasma renin decreased with age in patients with renovascular hypertension and essential hypertension. However, in patients with renovascular hypertension, the change was not statistically significant. Plasma aldosterone concentration showed a tendency to decrease with age in both groups. Stimulated plasma renin activity and the net increase in plasma renin activity after captopril administration in patients with essential hypertension showed a significant decrease with age. In patients with renovascular hypertension, exaggerated response of renin secretion was observed in younger patients, but middle-aged and elderly patients did not demonstrate this hyper-responsiveness. The degree of decrease in blood pressure by administration of an angiotensin (Ang) II analog ([Sar1,Ile8] Ang II) was the same in both younger and elderly patients with either disease. These results suggest that the effect of aging on the RAS occurs not only in patients with essential hypertension, but also in patients with renovascular hypertension. Furthermore, although the Ang II analog infusion test and captopril stimulation test are considered to be useful screening tests for renovascular hypertension, we consider that the combination of Ang II analog test and captopril test may be favorable to screen renovascular hypertension, since the captopril stimulation test had a lower sensitivity in younger (under 35 years old) patients.
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PMID:Effect of aging on the renin angiotensin system in patients with renovascular hypertension. 161 67

Pinacidil, an antihypertensive agent that opens potassium channels, lowers plasma aldosterone levels in hypertensive patients by an unknown mechanism. In the present study, pinacidil's direct effects on production of aldosterone were assessed using isolated cells from bovine adrenal glomerulosa. Pinacidil was found to inhibit aldosterone production, both basally and during stimulation with either potassium, angiotensin II (Ang II), or adrenocorticotropic hormone (p less than 0.001), with half maximal inhibition occurring at 10(-5) M. As assessed by the exclusion of trypan blue from cells, pinacidil did not inhibit secretion through injurious effects on glomerulosa cells. Also, washing of cells previously exposed to pinacidil restored secretory responsiveness. Pinacidil did not alter cytosolic calcium (Ca2+) concentrations when aequorin was used as a photoluminescent indicator of Ca2+ levels, suggesting that pinacidil acted by a non-Ca(2+)-mediated mechanism. Consistent with direct inhibition of the late pathway in steroidogenesis was that pinacidil decreased conversion of pregnenolone and corticosterone to aldosterone. Pinacidil did not block binding of Ang II to its receptor, nor did it appear to affect adrenocorticotropic hormone-receptor binding, since stimulation by cyclic AMP, the post-receptor second messenger of adrenocorticotropic hormone, was also inhibited. In summary, pinacidil inhibited directly the adrenal's production of aldosterone. The mechanism whereby the inhibition occurred was unclear.
Hypertension 1991 Oct
PMID:Inhibition of aldosterone production by pinacidil in vitro. 165 50

Evidence was sought for beta-adrenergic-induced increase in femoral vascular angiotensin production in sham-operated and nephrectomized rabbits. Systemic blood pressure and right femoral blood flow were monitored in anesthetized rabbits. Arterial and femoral venous plasma angiotensin II (Ang II) and angiotensin I (Ang I) were measured by radioimmunoassay after high-performance liquid chromatography. Isoproterenol, 1 and 10 nmol/min, was infused intrafemoral arterially, reducing femoral vascular resistance by 47 +/- 5% and 60 +/- 6% in the sham-operated group, and by 50 +/- 6% and 63 +/- 4% in the nephrectomized group, respectively. The hemodynamic effect of isoproterenol was blocked by 2 mumol/kg propranolol injected intravenously plus 0.2 mumol/min infused intrafemoral arterially, indicating that the effect was beta-adrenergically mediated. In the sham-operated group, arterial Ang II and Ang I levels were increased, respectively, by 85 +/- 16% and 103 +/- 23% with the low dose of isoproterenol, and by 121 +/- 13% and 563 +/- 126% with the high dose of isoproterenol. The apparent femoral Ang II secretion rate was increased by 3.2-fold and 4.4-fold, and the apparent femoral Ang I secretion rate increased by 4.3-fold and 21.2-fold, with the low and high dose of isoproterenol, respectively. Propranolol abolished or markedly attenuated the increased arterial angiotensin levels and the increased femoral angiotensin secretion rates. Neither the low nor the high dose of isoproterenol caused any increase in plasma levels or the apparent femoral secretion rates of the angiotensins in the nephrectomized group. Low plasma levels of Ang I and Ang II remained in the nephrectomized group, representing some locally generated angiotensins.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1991 Jun
PMID:Beta-adrenergic-induced local angiotensin generation in the rabbit hind limb is dependent on the kidney. 167 1

In recent years, the role of the renin-angiotensin system (RAS) in the development of hypertension has been investigated extensively. Studies have shown that there are actually two systems: a tissue and a circulating RAS. The control of hypertension is focused primarily in the RAS in the cardiovascular system and the brain. By manipulating the RAS with angiotensin converting enzyme (ACE) inhibitors, researchers have learned that the cardiovascular neuronal centers in the brain have receptor sites for the actions of angiotensin II (Ang II). Receptors for Ang II are found in the medulla oblongata in neurons involved in the regulation of baroceptor activity. Since studies in both animals and hypertensive patients indicate that ACE inhibitors reduced sympathetic activity and enhanced baroceptor sensitivity, it is possible that the primary hypotensive mechanism of these agents is through blockage of Ang II formation in the cardiovascular centers of the brain.
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PMID:The renin-angiotensin system: importance in physiology and pathology. 169 11


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