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

Abstract

The present study was performed to evaluate renal vascular responsiveness (RVR) to ANG II in hypertensive transgenic rats [TGR; strain TGR(mRen2)27] harboring the mouse ren-2 renin gene. Renal blood flow (RBF) responses to either intravenous or intrarenal arterial administration of ANG II were assessed in pentobarbital sodium-anesthetized female heterozygous TGR (9–12 wk old) and age-matched transgene-negative Hanover Sprague-Dawley rats (HanSD). Intravenous bolus injections of 15 and 30 ng ANG II elicited dose-dependent increases in mean arterial blood pressure (AP) and decreases in RBF in both 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 the decrease in RBF elicited by intravenous administration of 15 ng of ANG II was greater in TGR than HanSD (−62 ± 3 vs. −52 ± 5%, P < 0.05). Intrarenal 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 norepinephrine (40 and 80 ng) elicited smaller decreases in RBF in TGR than in HanSD (−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 increase in RVR to endogenous vasoconstrictors. Furthermore, the enhanced RVR to ANG II does not appear to reflect an impaired RVR to endogenous vasodilator factors since intrarenal administration of bradykinin and acetylcholine elicited larger increases in RBF in TGR than in HanSD. The present findings indicate that hypertensive TGR exhibit exaggerated renal and peripheral vascular responses to ANG II, which likely contributes to an increased renal and peripheral vascular resistance and thereby to the hypertension in TGR.

Effects of Dietary Salt Load and Salt Depletion on the Course of Hypertension and Angiotensin II Levels in Male and Female Heterozygous Ren-2 Transgenic Rats

“…We found, in accordance with recent studies, that TGR exhibit an augmented peripheral and renal vascular responsiveness to ANG II at all ages and independently of sodium balance when compared with age-matched HanSD rats [5,58] . However, these peripheral and renal vascular responses to ANG II were comparable in female and male TGR.…”

The Roles of Intrarenal 20-Hydroxyeicosatetraenoic and Epoxyeicosatrienoic Acids in the Regulation of Renal Function in Hypertensive Ren-2 Transgenic Rats

“…However, the exact pathophysiological mechanism(s) leading to the development and maintenance of hypertension in TGR are still far from understood. We and others [16,17] have demonstrated that TGR exhibit enhanced peripheral and renal vasoconstrictor responsiveness specifically to ANG II when compared with transgene-negative normotensive Hannover Sprague-Dawley (HanSD) rats. In addition, Mitchell and Mullins [18] have shown that TGR have exaggerated tubuloglomerular feedback responsiveness and that ANG II exerts an important stimulatory influence on their sensitivity.…”

Acute Effects of Cyclooxygenase-2 Inhibition on Renal Function in Heterozygous Ren-2-Transgenic Rats on Normal or Low Sodium Intake

“…However, it has been reported that TGR exhibit an enhanced peripheral and renal vascular responsiveness to ANG II [7]. It is well known that the vasodilator prostanoids, the products of the cyclooxygenase (COX) pathway of the arachidonic acid metabolism, oppose the effects of the renal vasoconstrictor actions of ANG II [8, 9; for review see 10].…”