Two-Kidney, One-Clip Hypertension in the Rat

Baroreflex function was studied in conscious early phase (<6 weeks) two-kidney, one-clip hypertensive rats before and 24 hours after surgical reversal of hypertension by removal of the constricting renal artery clip or after pharmacological reduction of blood pressure by an infusion of hydralazine or captopril. A normotensive sham-clipped group was included. Another group of two-kidney, one-clip rats was studied 3 weeks after unclipping. Baroreflex sensitivity, as assessed by the steady-state method using a graded phenylephrine infusion, mean arterial pressure, and heart rate were measured preoperatively and at 24 hours postoperatively. Two-kidney, one-clip rats were significantly hypertensive preoperatively compared with control (mean arterial pressure, 183 ±4 vs. 106±2 mm Hg,p<0.001), heart rate was similar (420±9 vs. 401± 9 beats/min, p>0.05), and baroreflex sensitivity was significantly reduced (0.76±0.07 vs. 1.50+±0.20 msec/mm Hg; p<0.001). There was a minimal change in heart rate despite the fall in mean arterial pressure in all hypertensive groups, indicating resetting of the baroreflexes. At 24 hours after the operation, baroreflex sensitivity was unchanged in all groups compared with the preoperative value. By 3 weeks, baroreflex sensitivity was significantly greater than in the hypertensive two-kidney, one-clip rats before the operation and 24 hours after they were unclipped, but not compared with normotensive sham-clipped rats. Thus, although resetting occurs within 24 hours, whatever the method of blood pressure reduction, baroreflex sensitivity remains impaired at this time. However, baroreflex sensitivity had returned to normal at 3 weeks after the rats were unclipped, suggesting the importance of structural change. These baroreflex alterations appear to be independent of the renin-angiotensin system but consequential to the fall in blood pressure. (Circulation Research 1990;66:1673-1680)