Differing effects of enalapril and losartan on renal medullary blood flow and renal interstitial hydrostatic pressure in spontaneously hypertensive rats.

Objective To determine the effect of short-term angiotensin converting enzy me inhibition (enalapril) or angiotensin II AT(1) receptor blockade (losart an) on medullary hemodynamics in the spontaneously hypertensive rat (SHR). Design Laser-Doppler flowmetry allowed for the characterization of medullar y blood flow (MBF) over a wide range of renal arterial pressure (RAP), and was used for comparison among treatment groups. Renal interstitial hydrosta tic pressure (RIHP) was also determined over a wide range of RAP. Method: Enalapril or losartan was given to male 12-13-week-old SHR for 3 da ys (25 mg/kg per day in drinking water). Rats were anesthetized with Inacti n, renal function was measured at resting levels of RAP and then RAP was va ried over a range of 50-150 mmHg in 25 mmHg steps. MBF and RIHP were determ ined at each pressure. Results Resting mean arterial pressure (MAP) (mmHg +/- SE) for enalapril- a nd for losartan-treated SHR [114 +/- 3 (n = 18) and 124 +/- 3 (n = 20), res pectively] were both significantly lower than for untreated SHR [159 +/- 5 (n = 20)]. Renal function at resting levels of MAP was not significantly di fferent among groups. Enalapril and losartan both increased MBF by 30% at l evels of RAP of 125 mmHg and over. Enalapril did not alter the relation bet ween RAP and RIHP, but losartan shifted the RAP versus RIHP curve by approx imately 40 mmHg to lower levels of RAP. Acute administration of the B2 kini n receptor antagonist HOE 140 [20 mu g/kg intravenous (i.v.) bolus, then 10 mu g/kg per h i.v.] did not significantly alter MAP in any group. HOE 140 did not significantly alter MBF or RIHP in the untreated or losartan-treate d SHR. MBF in enalapril-treated rats receiving HOE 140 was not significantl y different from that of the enalapril-only group; however, the relation be tween RAP and RIHP was shifted to lower levels of RAP by approximately 45 m mHg. Conclusions Both enalapril and losartan increase MBF in SHR, suggesting tha t the medullary circulation of SHR is influenced by endogenous levels of an giotensin II. The failure of enalapril to increase RIHP in parallel with MB F appears to be due to an enhanced effect of kinins. I Hypertens 1999, 17:1 345-1352 (C) Lippincott Williams & Wilkins.