摘要:

We compared the ability of angiotensin II (Ang II) to induce hypertrophy of neonatal rat ventricular myocytes with that of endothelin-1. Over 72 hours, Ang II (1 micro mol/L) increased the ratio of protein to DNA by less than 10%, whereas endothelin-1 (100 nmol/L) produced a 28% increase. The growth effects of either agonist occurred independently of chronotropic actions. Radioligand binding studies showed that myocytes have nearly 300-fold more receptors for endothelin-1 than Ang II, and type 1 and type 2 Ang II receptor subtypes (AT1and AT (2)) are present in near equal proportions. Cotreatment with a 10-fold molar excess of AT2antagonists (PD 123177 or CGP 42112) for 72 hours augmented the Ang II-induced increase in the protein-to-DNA ratio to levels nearly as high (23%) as those with endothelin-1 (28%). AT2antagonists enhanced Ang II stimulation of protein synthesis, as indexed by [(3) Hydrogen]leucine incorporation, whereas an AT antagonist blocked Ang II-induced incorporation. An AT2antagonist also prevented Ang II-induced protein degradation. In conclusion, Ang II-induced myocyte growth is tempered because of low AT1levels and an antigrowth effect of AT2. These findings have potential clinical significance in that regression of hypertension-induced cardiac hypertrophy by AT1antagonists may be in part due to an unopposed antigrowth effect of Ang II mediated via AT2. (Hypertension. 1996;28:635-640.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Our primary aim in the present study was to investigate the association between blood pressure measured in the laboratory and in the ambulatory state in a group of middle-aged borderline hypertensive men and age-matched normotensive control subjects. In addition, we examined the relation between stress-induced blood pressure measurements and left ventricular mass. Blood pressure and heart rate were measured noninvasively during a standardized laboratory stress protocol and four times per hour throughout 24 hours. Borderline hypertensive subjects had significantly higher systolic and diastolic pressures than normotensive subjects during both the daytime (systolic pressure, 141.1 plus/minus 9.7 versus 130.9 plus/minus 8.6 mm Hg; diastolic pressure, 88.8 plus/minus 7.0 versus 79.4 plus/minus 6.2 mm Hg, P < .001) and nighttime (systolic pressure, 114.0 plus/minus 9.9 versus 107.1 plus/minus 8.3 mm Hg; diastolic pressure, 71.5 plus/minus 7.5 versus 64.6 plus/minus 7.2 mm Hg, P < .001). The borderline hypertensive group also displayed increased systolic pressure reactivity in the laboratory compared with the normotensive group. The groups did not differ significantly in left ventricular mass (index). In both borderline hypertensive and normotensive individuals, blood pressure levels during stress testing were closely related to ambulatory blood pressure levels (r = .51 to .82). Furthermore, stress-induced blood pressure levels were significantly correlated to left ventricular mass in borderline hypertensive (r = .33 to .40) but not normotensive subjects. Since stress-induced blood pressure levels were significantly associated with both ambulatory blood pressure levels and left ventricular mass in borderline hypertensive subjects, the addition of standardized stress testing to casual blood pressure measurements may improve risk estimation. (Hypertension. 1996;28:641-646.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

We undertook this prospective double-blind, placebo-controlled study to evaluate the efficacy and safety of low-dose (15 mg) pravastatin in elderly hypercholesterolemic hypertensive subjects with concurrent antihypertensive treatment and to determine whether fasting hyperinsulinemia could also be improved. At three hypertension and lipid clinics of two medical centers, 96 elderly (49 women, 47 men) ambulatory subjects were randomized to active treatment or placebo for 12 months after a 3-month single-blind lead-in period. Hypertensive subjects with plasma total cholesterol levels of at least 6.47 mmol/L (250 mg/dL) and triglyceride levels less than 3.39 mmol/L (300 mg/dL) were treated with 15 mg pravastatin for 12 months after receiving 3 months of the American Heart Association step I diet. Lipid, glucose, and fasting insulin levels were measured; clinical laboratory tests included liver function and creatine kinase determinations. After 12 months of pravastatin therapy, plasma total cholesterol concentration decreased by 25.1% (from a mean of 7.29 to 5.47 mmol/L, P < .05), low-density lipoprotein cholesterol decreased by 30.2% (from 5.27 to 3.68 mmol/L, P <.05), and triglycerides decreased by 10.7% (from 1.68 to 1.50 mmol/L, P <.05). High-density lipoprotein cholesterol increased by 9.2% (from 1.20 to 1.31 mmol/L, P < .05). Fasting insulin levels decreased from 89.0 to 61.5 pmol/L (P < .05). All of these changes were greater (P < .05) than any tendency toward change in the placebo group. Adverse events and clinical laboratory abnormalities were generally mild and transient in both placebo and pravastatin groups. Study drugs were withdrawn from one subject in each group with asymptomatic creatine kinase elevations. We conclude that low-dose pravastatin was effective and safe in the treatment of hypercholesterolemic hypertensive subjects on concurrent antihypertensive therapy. It also improved fasting hyperinsulinemia despite the use of beta-blockers and diuretics in these hypertensive subjects. (Hypertension. 1996;28:647-651.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Hypertension is more prevalent in blacks than whites, and the reasons for this difference remain unclear. To test whether endothelin may play a role in these racial variations, we analyzed plasma samples from black and white women and men with high blood pressure by an enzyme-linked immunoassay specific for endothelin-1 (ET-1), a potent vasoconstrictor, and compared them with those obtained from similar subjects with normal blood pressure. Both female and male hypertensive blacks had elevated levels of immunoreactive ET-1 (11.3 plus/minus 1.0 and 12.3 plus/minus 1.3 nmol/L, respectively) compared with values in normotensive control blacks (1.5 plus/minus 0.2 and 1.4 plus/minus 0.2 nmol/L). Corresponding values in female and male hypertensive whites were 3.8 plus/minus 0.6 and 3.8 plus/minus 0.6 nmol/L, respectively, compared with respective values of 1.4 plus/minus 0.1 and 2.8 plus/minus 0.4 nmol/L in normotensive control whites. These results indicate that plasma concentrations of immunoreactive ET-1 levels differ significantly between black and white individuals with high blood pressure. This finding may be an important factor in the etiology of racial differences in the prevalence and severity of hypertension and deserves further study. (Hypertension. 1996;28:652-655.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The hypotensive effect of correction of renal artery stenosis in humans or experimental animals with renovascular hypertension is commonly attributed to decreasing renin secretion from the formerly stenotic kidney. However, plasma renin activity is normal in 50% of individuals with renovascular hypertension. We studied conscious, chronically instrumented two-kidney, one clip (2K1C) rats. The renal artery clip was removed and mean arterial pressure measured for 3 days. The majority of the fall in blood pressure occurred between 2 and 48 hours after unclipping. Measurement of water balance and urinary sodium excretion revealed no effect of unclipping. In another experiment, 2K1C hypertensive rats were chronically treated with enalapril and concomitant infusion of angiotensin II (3.8 pmol/min [4 ng/min] IV) to maintain blood pressure at hypertensive levels and prevent a fall in angiotensin II levels on unclipping. After 5 days, the clip was removed or sham removed, and treatment was continued. Blood pressure was recorded for 7 days. Blood pressure remained elevated in the sham unclipped rats. Unclipped rats exhibited a dichotomous response: blood pressure fell significantly within 48 hours in the majority of rats (responders) but remained elevated in a minority (nonresponders). All treatment was then withdrawn for 2 days. Sham unclipped rats remained hypertensive, and responders exhibited a further small decline in blood pressure. Blood pressure fell to normal in the nonresponders. Blood pressure falls after correction of renal artery stenosis in renovascular hypertension in part because of a decrease in pressor responsiveness to angiotensin II. (Hypertension. 1996;28:656-662.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

We investigated the ability of angiotensin II (Ang II) or the stable analogue [Sar1]-Ang II to increase intracellular and extracellular free arachidonic acid in primary cultures of rabbit proximal tubular epithelial cells to better characterize the receptor subtype and orientation of phospholipase A2(PLA2)-mediated signaling. Proximal tubular cells were labeled with [(3) Hydrogen]arachidonic acid for 4 hours and then treated with Ang II or [Sar1]-Ang II. Lipids were extracted from labeled cells, separated by thin-layer chromatography, and quantified by liquid scintillation counting. Ang II (10 micro mol/L, 1 minute) stimulated an increase in intracellular free [(3) Hydrogen]arachidonic acid from 21.0 plus/minus 2.0 to 32.2 plus/minus 2.8 disintegrations per minute/micro gram protein, an effect that was potentiated by EGTA. [Sar1]-Ang II stimulated a time- and concentration-dependent increase in [(3) Hydrogen]arachidonic acid release from labeled cells. Release of [(3) Hydrogen]arachidonic acid was maximal at 10 micro mol/L [Sar1]-Ang II, with an EC50of approximately 3 micro mol/L. Ang II receptor antagonists caused concentration-dependent inhibition of [Sar1]-Ang II-stimulated [(3losartan. Furthermore, in proximal tubular epithelial cells grown on polyester membrane filters, the Ang II receptor that mediated arachidonic acid release was predominantly apical rather than basolateral. These observations are consistent with activation of a Calcium2+-independent, apical PLA2isoform in epithelial cells through an Ang II type 2 receptor subtype. (Hypertension. 1996;28:663-668.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Chronic low-dose angiotensin II (Ang II) infusion for 13 days mimics two-kidney, one clip Goldblatt hypertension and increases intrarenal Ang II levels. We performed studies to determine the time course for the enhancement of intrarenal Ang II levels and whether the increased intrarenal Ang II is a tissue-specific event and requires a receptor-mediated step. Male Sprague-Dawley rats were uninephrectomized, and either vehicle or Ang II (40 ng/min) was infused via a subcutaneous osmotic minipump. Plasma and renal Ang II levels were measured 3, 7, 10, and 13 days after minipump implantation. Compared with controls (126 plus/minus 2 mm Hg), systolic pressure in Ang II-infused rats exhibited a detectable increase by day 6 (146 plus/minus 2 mm Hg) and continued to increase to 189 plus/minus 5 mm Hg by day 12. Plasma Ang II levels were elevated by day 3, whereas intrarenal Ang II levels were not significantly elevated until 10 days of Ang II infusion. Renal injury characterized by focal and segmental glomerulosclerosis was evident after 13 days of Ang II infusion. Losartan (30 mg/kg per day) prevented the development of hypertension in the Ang II-infused rats for the duration of the infusion period (125 plus/minus 1 mm Hg) and reduced the degree of glomerular injury. Plasma renin activity was suppressed in the Ang II-infused group but was elevated markedly in both losartan-treated groups. Plasma Ang II levels were elevated in the Ang II-infused rats and were even higher during losartan treatment. Intrarenal Ang II levels were enhanced significantly (354 plus/minus 60 versus 164 plus/minus 23 fmol/g) in the Ang II-infused rats. However, losartan treatment prevented the augmentation of intrarenal Ang II caused by Ang II infusion. Heart and adrenal Ang II levels were not significantly increased in the Ang II-infused rats but were significantly elevated during losartan treatment. These results suggest that the tissue-specific elevations of intrarenal Ang II levels caused by chronic Ang II infusion are mediated by angiotensin type 1 receptor activation, which leads to either receptor-mediated internalization of Ang II, enhancement of intrarenal Ang II formation, or both. (Hypertension. 1996;28:669-677.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

To investigate angiotensinogen regulation in high-renin hypertension, we infused porcine renin intravenously at either a low (4 mU/kg per hour, n = 6) or high (20 mU/kg per hour, n = 9) dose into male Sprague-Dawley rats (225 to 250 g) for 5 days using osmotic minipumps. Control rats received 0.9% NaCl. In renin-infused rats, mean arterial pressure and plasma renin activity were significantly elevated. Both low- and high-renin infusions lowered plasma angiotensinogen levels. Plasma angiotensin II was elevated in rats given renin but reached statistical significance only at the higher dose. Angiotensinogen mRNA isolated from the liver, adrenal gland, kidney, and brain was measured by slot blot analysis. Both renin doses were associated with significant decreases in the levels of liver and hypothalamic angiotensinogen mRNA. In the medulla oblongata, angiotensinogen mRNA was reduced only by the higher renin dose. The lower dose increased angiotensinogen mRNA in the adrenal gland, and in kidney, angiotensinogen mRNA level was unchanged by renin infusion. Angiotensinogen mRNA visualized on Northern blots showed that the number of mRNA species in liver decreased from three in control rats to a single mRNA species after renin infusion. Tissue differences in the size of the major angiotensinogen mRNA species were also apparent. This, together with changes in the total hybridization signal of angiotensinogen mRNA in tissues, suggests that renin differentially affects the different angiotensinogen mRNA transcripts. Results of this study indicate that angiotensinogen gene expression is regulated not only by alterations in levels of circulating angiotensin II but also by other mechanisms, presently unidentified, that are activated by renin infusions. (Hypertension. 1996;28:678-681.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

We studied the effects of the endogenous cannabinoid ligand anandamide on blood pressure, single unit activity of barosensitive neurons in the rostral ventrolateral medulla, and postganglionic splanchnic sympathetic nerve discharge in urethane-anesthetized rats. In rats with an intact baroreflex, an intravenous bolus of 4 mg/kg anandamide caused a triphasic blood pressure response: transient hypotension, followed by a brief pressor and more prolonged depressor phase. Anandamide evoked a "primary" increase in neuronal firing coincident with its pressor effect and a "secondary," baroreflex-mediated rise coincident with its depressor effect at both sites. Pretreatment of rats with phentolamine or trimethaphan did not inhibit either the pressor response or the primary increase in splanchnic nerve discharge elicited by anandamide. In barodenervated rats, electrical stimulation of the rostral ventrolateral medulla increased blood pressure and splanchnic nerve discharge. Anandamide treatment blunted the rise in blood pressure without affecting the increase in splanchnic nerve discharge. Anandamide did not affect the rise in blood pressure in response to an intravenous bolus dose of phenylephrine. The results indicate that (1) the brief pressor response to anandamide is not sympathetically mediated, and (2) the prolonged hypotensive response to anandamide is not initiated in the central nervous system, in ganglia, or at postsynaptic adrenergic receptors but is due to a presynaptic action that inhibits norepinephrine release from sympathetic nerve terminals in the heart and vasculature. (Hypertension. 1996;28:682-686.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID