Whole body vascular reactivity during the development of deoxycorticosterone acetate hypertension in the pig

Abstract

A change in vascular reactivity was characterized in the pig during the development of deoxycorticosterone acetate (DOCA) hypertension. Pigs, 8-12 weeks of age, were subjected to unilateral nephrectomy and instrumented with an electromagnetic flowprobe on the ascending aorta and with Tygon catheters in the aorta and thoracic vena cava. Approximately 2 weeks after surgery, Silastic strips impregnated with DOCA (100 mg/kg) were implanted subcutaneously. Within the first 3 days after implantation, mean arterial pressure (MAP) began to rise and reached levels approximately 40% greater than control during the 4th week. Graded intravenous infusions of norepinephrine or angiotensin II were given to unanesthetized pigs before, and at intervals during, the development of hypertension. Changes in total peripheral resistance were calculated from recordings of MAP and cardiac output. Comparison of pre-DOCA response curves with those obtained at intervals following DOCA implantation demonstrated a significant increase in vascular smooth muscle sensitivity (decrease in threshold infusion rates) to both drugs post-DOCA. There also was a shift to the left in the dose-response curves. These changes in systemic vascular reactivity occurred at the time the arterial pressure began to rise. The temporal relationship suggests that the increase in vascular reactivity may initiate the increase in mean arterial pressure.