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-1 (ET-1), as well as vascular reactivity to exogenous ET-1 and to insulin, were compared in hypertensive and normotensive subjects. Peripheral vascular release of AII and of ET-1 was investigated in 10 hypertensive (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 was calculated from the respective Arterio-Venous (A-V) differences in plasma concentrations (PC) of the peptides and the regional plasma flow (indocyanine-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 insulin, 1 mU/kg/min) in 7H and 7N. Moreover, hemodynamic changes to sequential exogenous ET-1 infusion (1, 2.5, 5, 10, 20, 40 ng/min) or during hyperinsulinemic 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 two subject groups. The cold stimulus provoked a similar increase in transfemoral 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 ± SD, P< .05). In contrast, the cold-induced increase in transfemoral AII release was somewhat more 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 value H v N P< .05). During the hyperinsulinemic clamp the PC of insulin increased from 5.8 ± 2.8 to 69.1 ± 15.5 μU/mL in H and from 4.6 ± 1.7 to 67.5 ± 9,5 μU/mL in N; P< .0005. Hyperinsulinemia induced a similar elevation of norepinephrine PC in H and N, but an increase in transfemoral 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 of AII is more pronounced in H than in N, whereas insulin provokes an increase in AII formation in hypertensives only. Moreover, insulin-mediated vasodilation and ET-1-dependent vasoconstriction are blunted in hypertensive subjects.