Attenuated renal vascular responses to acute angiotensin II infusion in smooth muscle-specific Na+/Ca2+exchanger knockout mice

Abstract

Recent studies in smooth muscle-specific Na+/Ca2+exchanger-1 knockout (NCX1sm−/−) mice reveal reduced arterial pressure and impaired myogenic responses compared with heterozygous littermates. In this study, we determined renal function in male anesthetized NCX1sm−/−mice and NCX1 heterozygous (NCX1+/−) littermates before and during acute ANG II infusions. Systolic blood pressure in awake mice was lower in NCX1sm−/−mice compared with NCX1+/−mice (119 ± 4 vs. 131 ± 3 mmHg, P < 0.05). Acute ANG II infusions (5 ng·min−1·g−1body wt) increased mean arterial pressure in anesthetized NCX1+/−(109 ± 2 to 134 ± 3 mmHg, P < 0.001, n = 8) and NCX1sm−/−(101 ± 8 to 129 ± 8 mmHg, P < 0.01, n = 6) mice to a similar extent (Δ25 ± 1 vs. Δ28 ± 4 mmHg, P > 0.05). In response to ANG II infusions, PAH clearance (CPAH) decreased from 1.39 ± 0.27 to 0.98 ± 0.22 ml·min−1·g−1( P < 0.05) and glomerular filtration rate (GFR) was reduced from 0.50 ± 0.09 to 0.32 ± 0.06 ml·min−1·g−1( P < 0.05) in NCX1+/−mice. In contrast, the NCX1sm−/−did not exhibit significant reductions in either CPAH(1.16 ± 0.30 to 1.22 ± 0.34 ml·min−1·g−1, P > 0.05) or GFR (0.48 ± 0.08 to 0.41 ± 0.05 ml·min−1·g−1, P > 0.05) during acute ANG II infusions. Using flometry to measure renal blood flow continuously, NCX1sm−/−mice had significantly attenuated responses to ANG II infusions (−34.2 ± 3.9%, P < 0.05) compared with those in NCX1+/−mice (−48 ± 2%) or in wild-type mice (−69 ± 7%). These data indicate that renal vascular responses to ANG II are attenuated in NCX1sm−/−mice compared with NCX1+/−mice and that NCX1 contributes to the renal vasoconstriction response to acute ANG II infusions.