Enhanced renal vascular responsiveness to angiotensin II in hypertensive ren-2 transgenic rats

The present study was performed to evaluate renal vascular responsiveness ( RVR) to ANG II in hypertensive transgenic rats [TGR; strain TGR(mRen2)27] h arboring the mouse ren-2 renin gene. Renal blood flow (RBF) responses to ei ther intravenous or intrarenal arterial administration of ANG II were asses sed in pentobarbital sodium-anesthetized female heterozygous TGR (9-12 wk o ld) and age-matched transgene-negative Hanover Sprague-Dawley rats (HanSD). Intravenous bolus injections of 15 and 30 ng ANG-II elicited dose-dependen t increases in mean arterial blood pressure (AP) and decreases in RBF in bo th TGR and HanSD. However, the magnitude of the increases in AP was greater in TGR than in HanSD (24 +/- 1 vs. 17 +/- 2 mmHg and 33 +/- 2 vs. 25 +/- 1 mmHg, respectively, P < 0.05 in both cases). Similarly: the magnitude of t he decrease in RBF elicited by intravenous administration of 15 ng of ANG I I was greater in TGR than HanSD (-62 +/- 3 vs. -52 +/- 5%, P < 0.05). Intra renal arterial administration of 1.5 and 3 ng ANG II did not alter mean AP in either group but elicited larger decreases in RBF in TGR than in HanSD ( -24 +/- 2 vs. -13 +/- 1% and -41 +/- 5 vs. -30 +/- 2%, respectively, P < 0. 05 in both cases). In contrast, intrarenal arterial administration of norep inephrine (40 and 80 ng) elicited smaller decreases in RBF in TGR than in H anSD (-24 +/- 3 vs. -40 +/- 6% and -51 +/- 9 vs. -71 +/- 8%, respectively, P < 0.05 in both cases), indicating that TGR do not exhibit a generalized i ncrease in RVR to endogenous vasoconstrictors. Furthermore, the enhanced RV R to ANG II does not appear to reflect an impaired RVR to endogenous vasodi lator factors since intrarenal administration of bradykinin and acetylcholi ne elicited larger increases in RBF in TGR than in HanSD. The present findi ngs indicate that hypertensive TGR exhibit exaggerated renal and peripheral vascular responses to ANG; II, which likely contributes to an increased re nal and peripheral vascular resistance and thereby to the hypertension in T GR.