Abstract
Pendrin is a Cl−/HCO3 − exchanger expressed in the apical regions of renal intercalated cells. Following pendrin gene ablation, blood pressure falls, in part, from reduced renal NaCl absorption. We asked if pendrin is expressed in vascular tissue and if the lower blood pressure observed in pendrin null mice is accompanied by reduced vascular reactivity. Thus, the contractile responses to KCl and phenylephrine (PE) were examined in isometrically mounted thoracic aortas from wild-type and pendrin null mice. Although pendrin expression was not detected in the aorta, pendrin gene ablation changed contractile protein abundance and increased the maximal contractile response to PE when normalized to cross sectional area (CSA). However, the contractile sensitivity to this agent was unchanged. The increase in contractile force/cross sectional area observed in pendrin null mice was due to reduced cross sectional area of the aorta and not from increased contractile force per vessel. The pendrin-dependent increase in maximal contractile response was endothelium- and nitric oxide-independent and did not occur from changes in Ca2+ sensitivity or chronic changes in catecholamine production. However, application of 100 nM angiotensin II increased force/CSA more in aortas from pendrin null than from wild type mice. Moreover, angiotensin type 1 receptor inhibitor (candesartan) treatment in vivo eliminated the pendrin-dependent changes contractile protein abundance and changes in the contractile force/cross sectional area in response to PE. In conclusion, pendrin gene ablation increases aorta contractile force per cross sectional area in response to angiotensin II and PE due to stimulation of angiotensin type 1 receptor-dependent signaling. The angiotensin type 1 receptor-dependent increase in vascular reactivity may mitigate the fall in blood pressure observed with pendrin gene ablation.
Highlights
Pendrin is an electroneutral Cl2/HCO32 exchanger expressed in the apical regions of a minority cell type that localizes to the cortical collecting duct and connecting tubule in the kidney, where it mediates absorption of Cl2 and secretion of HCO32 [1,2,3,4]
Following 7 days of the NaCl-replete diet employed in this study, we observed previously that mean arterial pressure measured by telemetry is lower in pendrin null than in wild type mice [9,16]
Following 7 days of the NaCl-replete, gelled diet employed in this study, the present and previous studies have shown that mean arterial blood pressure is 5 to 9 mm Hg lower in pendrin null relative to wild type mice when measured by telemetry [9,16]
Summary
Pendrin is an electroneutral Cl2/HCO32 exchanger expressed in the apical regions of a minority cell type that localizes to the cortical collecting duct and connecting tubule in the kidney, where it mediates absorption of Cl2 and secretion of HCO32 [1,2,3,4]. Aldosterone and angiotensin II greatly stimulate pendrin abundance and function, thereby increasing renal Cl2 absorption, which contributes to the hypertension observed following the administration of these hormones [5,6,7]. Pendrin null mice have elevated plasma renin concentration [8,9], which should increase plasma angiotensin II concentration, thereby stimulating vascular contractility [15]. The purpose of this study was threefold: 1) to determine if pendrin is expressed in mouse aorta, 2) to determine if the lower blood pressure observed in pendrin null mice occurs in tandem with reduced vascular contractile function and 3) to ascertain the mechanism by which this occurs
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