SHORT-TERM EFFECTS OF ANGIOTENSIN-II BLOCKADE ON RENAL BLOOD-FLOW ANDSYMPATHETIC ACTIVITY IN AWAKE RATS

To investigate the effects of an angiotensin II type 1 receptor antago nist (CV-11974) on renal blood flow and renal sympathetic nerve activi ty compared with a calcium antagonist (nicardipine), we measured both parameters in conscious spontaneously hypertensive rats aged 13 to 15 weeks. One to 2 days after surgery, CV-11974 (n=9) and nicardipine (n= 8) were intravenously administered to decrease arterial pressure in a similar time course and degree of hypotension. CV-11974 increased rena l blood flow by 23+/-4% at the maximal fall in mean arterial pressure (-32+/-1 mm Hg), and renal nerve activity increased by 70+/-7%. The ma ximal increase in renal blood flow (+27+/-4%) was observed when mean p ressure was reduced by approximately 20 mm Hg. The maximal reduction o f renal vascular resistance (-33+/-3%) correlated significantly with p retreatment levels of plasma renin concentration (r=-.792). In contras t, nicardipine produced a progressive reduction of renal blood flow an d marked increases in heart rate and renal nerve activity. Increases i n heart rate and nerve activity were greater than those with CV-11974 treatment (P<.001). At the maximal fall in mean pressure (-32+/-1 mm H g), renal blood flow decreased by 23+/-4%, which was significantly cor related with percent changes in renal nerve activity (+150+/-11%, r=-. 744). Renal denervation in another set of rats (n=6) improved renal bl ood flow and renal vascular resistance responses to nicardipine. These results suggest that blockade of the angiotensin II type 1 receptor i ncreases renal blood flow with less sympathetic activation, whereas ca lcium antagonism decreases renal blood flow with reflex-mediated exace rbation of heart rate and renal nerve activity.