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Variation of plasma renin activity has been shown to occur during anesthesia, but its significance remains obscure. The recent development of a specific angiotensin II antagonist, saralasin, allows the delineation of the role of the renin-angiotensin system in blood pressure control during anesthesia. Twenty-seven rats were divided into four groups: awake, halothane (1 MAC), ketamine (125 mg/kg), and fluroxene (1 MAC). Arterial pressure was recorded continuously and plasma renin activity was determined by radioimmunoassay at the end of a two-hour awake control period, after one hour of anesthesia, and after half an hour of saralasin infusion. A similar protocol for enflurane with 1.75 vol per cent was also followed in seven anesthetized rats, but renin analysis was not performed.Anesthesia resulted in decreases in mean arterial pressure from 123.0 ± 1.3 torr to 95.2 ± 2.2 torr for ketamine, 91.6 ± 3.9 torr for halothane, 96.9 ± 7.9 torr for fluroxene, and 84.5 ± 3.8 torr for enflurane. Renin activity did not change significantly from control (4.33 ± 0.51 ng/ml/hr). When saralasin was infused only the rats anesthetized with halothane or enflurane had significant decreases in mean blood pressure, to 75.0 ± 4.8 and 66.1 ± 3.4 torr, respectively. It is concluded that the anesthetic agents studied do not cause a detectable increase in plasma renin activity. However, through the use of a competitive inhibitor of angiotensin II, a significant role for the maintenance of blood pressure by the renin-angiotensin system during halothane and enflurane anesthesia has been demonstrated.