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 actio n of an angiotensin II antagonist on the hyperglycemic response to hem orrhage (1.2 ml/100 g b.wt./2 min). The animals were divided into 3 ex perimental groups: (1) sham-operated animals submitted to intravenous administration of [1-Sar,8-Thr]-angiotensin II (sarthran), an antagoni st of angiotensin II (750 ng/100 g b,wt. as a bolus plus an infusion o f 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 hemorrhag e; (2) animals submitted to adrenodemedullation which decreased the hy perglycemic response to hemorrhage by 64% (P < 0.01). However, sarthra n infusion into adrenodemedullated rats caused a 38.5% further decreas e in hyperglycemic response to hemorrhage (P < 0.01); and (3) intact a nimals submitted to blockade of sympathetic noradrenergic pathways by treatment with guanethidine (10 mg/100 g b.wt.), which greatly decreas ed 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 hemorr hage by 34% (P < 0.01). Sarthran infusion into guanethidine-treated ra ts caused a further 34% decrease in hyperglycemic response to hemorrha ge (P < 0.01). These data indicate that angiotensin II has a direct hy perglycemic effect in addition to its action on sympathetic nervous sy stem activation and adrenomedullary secretion.