title: 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(+)/Ca(2+) exchanger-1 knockout (NCX1(sm-/-)) mice reveal reduced arterial pressure and impaired myogenic responses compared with heterozygous littermates. In this study, we determined renal function in male anesthetized NCX1(sm-/-) mice and NCX1 heterozygous (NCX1(+/-)) littermates before and during acute ANG II infusions. Systolic blood pressure in awake mice was lower in NCX1(sm-/-) mice compared with NCX1(+/-) mice (119 ± 4 vs. 131 ± 3 mmHg, P < 0.05). Acute ANG II infusions (5 ng·min(-1)·g(-1) body wt) increased mean arterial pressure in anesthetized NCX1(+/-) (109 ± 2 to 134 ± 3 mmHg, P < 0.001, n = 8) and NCX1(sm-/-) (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 (C(PAH)) 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 NCX1(sm-/-) did not exhibit significant reductions in either C(PAH) (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, NCX1(sm-/-) 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 NCX1(sm-/-) mice compared with NCX1(+/-) mice and that NCX1 contributes to the renal vasoconstriction response to acute ANG II infusions.
authors.affiliation: Department of Physiology and Hypertension and Renal Center of Excellence, Tulane Univ. Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Di
authors.initials: D
authors.lastname: Zhao
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.forename: Mordecai P
authors.initials: MP
authors.lastname: Blaustein
authors.forename: L Gabriel
authors.initials: LG
authors.lastname: Navar
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D012077:Renal Artery / Q000187:drug effects / Q000502:physiology*; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D019831:Sodium-Calcium Exchanger; D014662:Vasoconstrictor Agents; D000804:Angiotensin II