摘要:

Short-term infusions of angiotensin II (Ang II) increase renal vascular resistance and thereby endothelial shear stress and nitric oxide (NO) release. Prolonged stimulation of Ang II can decrease the expression of NO synthase isoforms in the macula densa, but prolonged increases in shear stress can increase transcription of endothelial NO synthase. Therefore, we designed these studies to test the hypothesis that Ang II exerts time-dependent effects on renal NO generation as assessed from renal excretion of nitrate and nitrite, percent increases in renal vascular resistance during inhibition of NO synthase with intravenous NG-nitro-L-arginine methyl ester (L-NAME), or decreases in renal vascular resistance during stimulation of endothelial NO synthase with intravenous acetylcholine. Rats were tested during graded short-term (30 to 90 minutes intravenous) or prolonged (5 to 6 days subcutaneous) Ang II infusions that led to dose-dependent increases in blood pressure and renal vascular resistance and reductions in renal blood flow. Captopril was administered for 3 to 4 days to suppress Ang II generation. The renal excretion of nitrate and nitrite was increased during short-term Ang II infusions (from 205 plus/minus 22 to 331 plus/minus 58 pmol [centered dot] min-1, P < .05) but was unchanged during prolonged Ang II infusion (control group, 197 plus/minus 33 versus Ang II, 245 plus/minus 42 pmol [centered dot] min-1, P = NS). The percent increase in renal vascular resistance with L-NAME was potentiated dose dependently by short-term but not long-term Ang II infusions. The increase in renal vascular resistance with L-NAME in control rats without Ang II infusions was +150 plus/minus 13%. At an Ang II infusion of 200 ng [centered dot] kg-1[centered dot] min-1, the L-NAME-induced percent increase in renal vascular resistance was significantly (P < .01) increased compared with controls in short-term Ang II-infused rats (+369 plus/minus 70%) but was not significantly different in prolonged infused rats (+190 plus/minus 33%). Intravenous acetylcholine caused dose-dependent renal vasodilation that was not significantly changed in rats receiving short-term intravenous Ang II but was significantly (P < .005) potentiated in those receiving prolonged Ang II infusions (change in renal vascular resistance with acetylcholine at 10 micro gram [centered dot] kg-1[centered dot] min-1versus control, -21.5 plus/minus 5.0%; with short-term Ang II, -24.9 plus/minus 4.5%; with long-term Ang II, -52.1 plus/minus 7.2%). In conclusion, short- and long-term Ang II infusions caused equivalent changes in blood pressure and renal blood flow and hence presumably equivalent increases in endothelial shear stress. However, only short-term Ang II infusions increased NO generation and the dependence of the renal circulation on NO, whereas acetylcholine-induced NO release was enhanced selectively during long-term Ang II infusions. This suggests that during long-term Ang II, renal NO release may become uncoupled from shear stress yet remains highly responsive to receptor-mediated stimulation. (Hypertension. 1996;27:1173-1179.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

To assess the role of insulin resistance in obesity hypertension, we examined the change of insulin sensitivity after weight loss in 24 obese hypertensive subjects by the euglycemic hyperinsulinemic glucose clamp method. The results of the 4-week calorie-restricted diet were a weight loss of 10.2% (from 74 plus/minus 12 to 67 plus/minus 11 kg, P < .01) and a decrease in mean blood pressure of 13.1% (from 124 plus/minus 7 to 107 plus/minus 9 mm Hg, P < .01). A decrease in plasma norepinephrine (from 208 plus/minus 74 to 142 plus/minus 52 pg/mL, P < .01) was associated with decreases in plasma renin activity (from 1.06 plus/minus 0.98 to 0.62 plus/minus 0.63 ng/mL per hour, P < .01) and serum aldosterone (from 70 plus/minus 28 to 57 plus/minus 24 pg/mL, P < .05). Glucose infusion rate increased significantly (42.9%), from 809 plus/minus 194 to 1155 plus/minus 251 micro mol/m2per minute. The insulin sensitivity index, which is a measure of the glucose infusion rate divided by plasma insulin, increased significantly (42.6%), from 10.8 plus/minus 3.5 to 15.4 plus/minus 4.4 (micro mol/m2per minute)/(micro U/mL). Stepwise multiple linear regression analysis showed that changes of plasma norepinephrine, insulin sensitivity index, plasma renin activity, and age were significant predictive factors for the change of mean blood pressure after weight loss. These results indicate a distinct relation between an improvement of insulin sensitivity and a decrease in blood pressure after weight loss in obese hypertensive subjects. The decrease in blood pressure after weight loss is probably related to the suppression of sympathetic nervous activity. (Hypertension. 1996;27:1180-1186.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID