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1 Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana 70112; and 2 Centre for Genome Research, University of Edinburgh, Edinburgh EH9 3JQ, United Kingdom
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.
acetylcholine; arterial blood pressure; bradykinin; endothelium-dependent vasodilators; hypertension; norepinephrine; renal blood flow; renal hemodynamics; renal vascular resistance
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