Effect of [1-Sar,8-Thr]-angiotensin II on the hyperglycemic response to hemorrhage in adrenodemedullated and guanethidine-treated rats.

The present experiments were designed to further investigate the action of an angiotensin II antagonist on the hyperglycemic response to hemorrhage (1.2 ml/100 g b.wt./2 min). The animals were divided into 3 experimental groups; (1) sham-operated animals submitted to intravenous administration of [1-Sar,8-Thr]-angiotensin II (sarthran), an antagonist of angiotensin II (750 ng/100 g b.wt. as a bolus plus an infusion of 25 ng/100 g b.wt./min over 30 min), which greatly attenuated (51.8% lower than controls; P < 0.01) the hyperglycemic response to hemorrhage; (2) animals submitted to adrenodemedullation which decreased the hyperglycemic response to hemorrhage by 64% (P < 0.01). However, sarthran infusion into adrenodemedullated rats caused a 38.5% further decrease in hyperglycemic response to hemorrhage (P < 0.01); and (3) intact animals submitted to blockade of sympathetic noradrenergic pathways by treatment with guanethidine (10 mg/100 g b.wt.), which greatly decreased the baseline value of plasma glucose (64.1 +/- 3.5 mg% vs. 125.3 +/- 4.5 mg%, P < 0.01), and reduced the hyperglycemic response to hemorrhage by 34% (P < 0.01). Sarthran infusion into guanethidine-treated rats caused a further 34% decrease in hyperglycemic response to hemorrhage (P < 0.01). These data indicate that angiotensin II has a direct hyperglycemic effect in addition to its action on sympathetic nervous system activation and adrenomedullary secretion.