Alterations in angiotensin II release and vascular reactivity in hypertensive men: A pilot study

Cold- and insulin-mediated release of angiotensin II (AII) and endothelin-l (ET-1), as well as vascular reactivity to exogenous ET-1 and to insulin, w ere compared in hypertensive and normotensive subjects. Peripheral vascular release of AII and of ET-1 was investigated in 10 hyper tensive (H; 29.2 +/- 5.8 years) and 12 normotensive (N; 29.1 +/- 4.6 years) men in two separate trials. Net transfemoral balance of AII and of ET-1 wa s calculated from the respective Arterio-Venous (A-V) differences in plasma concentrations (PC) of the peptides and the regional plasma now (indocyani ne-green dye method), both at baseline conditions and after a cold stimulus (immersion of one hand into ice water) in 7H and 6N, or during short-time hyperinsulinemia (hyperinsulinemic euglycemic clamp: biosynthetic human ins ulin, 1 mU/kg/min) in 7H and 7N. Moreover, hemodynamic changes to sequentia l exogenous ET-1 infusion (1, 2.5, 5, 10, 20, 40 ng/min) or during hyperins ulinemic clamp were studied in 7H and 6N and 7H and 7N, respectively. Baseline net-transfemoral balance of ET-1 and of AII were similar in the tw o subject groups. The cold stimulus provoked a similar increase in transfem oral ET-1 release in H and N (H: 257.0 +/- 31.7 to 526.2 +/- 393.7 pg/min; N: 280.2 +/- 112.7 to 524.0 +/- 393.7 pg/min, mean a SD, P < .05). In contr ast, the cold-induced increase in transfemoral AII release was somewhat mor e pronounced in H than in N (H: 162.2 +/- 304.6 to 1081.7 +/- 1037.7 pg/min , P < .05; N: 83.9 +/- 166.3 to 317.6 +/- 187.8 pg/min, P < .02; maximum va lue H upsilon N P < .05). During the hyperinsulinemic clamp the PC of insul in increased from 5.8 +/- 2.8 to 69.1 +/- 15.5 mu U/mL in H and from 4.6 +/ - 1.7 to 67.5 +/- 9.5 mu U/mL in N; P < .0005. Hyperinsulinemia induced a s imilar elevation of norepinephrine PC in H and N, but an increase in transf emoral ET-1 release in N only (219.7 +/- 161.2 to 512.2 +/- 279.0 pg/min, P < .02). In contrast, hyperinsulinemia increased transfemoral AII formation in H (730.4 +/- 554.3 to 1088.6 +/- 597.9 pg/min, P < .05), but not in N. Insulin-mediated vasodilation was observed only in N, whereas ET-1-induced vasoconstriction was blunted in H. We conclude that the cold-induced increase in peripheral vascular release o f AII is more pronounced in H than in N, whereas insulin provokes an increa se in AII formation in hypertensives only. Moreover, insulin-mediated vasod ilation and ET-1-dependent vasoconstriction are blunted in hypertensive sub jects. (C) 1999 American Journal of Hypertension, Ltd.