Short-Term Angiotensin Subtype 1 Receptor Blockade Does Not Alter the Circulatory Responses to Sympathetic Nervous System Modulation in Healthy Volunteers Before and During Sevoflurane Anesthesia: Results of a Pilot Study

Objective The mechanism of perioperative hypotension in patients taking an angiotensin-receptor blocker up to the time of surgery remains unclear. This study tested the hypothesis that short-term angiotensin-receptor blocker treatment attenuated the sympathetic and vascular responses to autonomic stimuli in volunteers undergoing anesthesia. Design Randomized, crossover, blinded, pilot design. Setting Zablocki Veterans Affairs Medical Center, Milwaukee, WI. Participants The study comprised 8 male and 6 female healthy, young volunteers (age 23±1.2 years [mean±standard error of the mean]). Interventions Volunteers were studied after receiving oral placebo or 50 mg of losartan (angiotensin-receptor blocker) for 3 days before each test day. The effectiveness of angiotensin-receptor blocker treatment was confirmed using the mean arterial blood pressure response to intravenous angiotensin II (1-µg bolus). Eight volunteers underwent direct mean arterial pressure and forearm bloodflow measurements during conscious baseline, a cold pressor test, induction of anesthesia, tracheal intubation, maintenance of anesthesia with 1 minimum alveolar concentration of sevoflurane, and airway irritation with 12% desflurane. Six volunteers experienced mean arterial pressure responses to 0.1 mg of phenylephrine at baseline and during 1 minimum alveolar concentration of sevoflurane. Measurements and Main Results Comparisons were made over time and across groups. Angiotensin-receptor blocker treatment significantly reduced-mean arterial pressure and forearm vascular resistance (forearm blood flow/mean arterial pressure) over time and blocked the mean arterial pressure response to angiotensin-II challenge. The changes in mean arterial pressure and forearm vascular resistance in response to all stressors did not differ between treatments. Mean arterial pressure increases from phenylephrine were preserved. Conclusions In healthy, young volunteers, sympathetically-mediated responses from the short-term use of an angiotensin-receptor blocker were not altered and most likely did not contribute to perioperative hypotension during the intraoperative period.