title: Differential effect of T-type voltage-gated Ca2+ channel disruption on renal plasma flow and glomerular filtration rate in vivo.
abstract: Voltage-gated Ca(2+) (Cav) channels play an essential role in the regulation of renal blood flow and glomerular filtration rate (GFR). Because T-type Cav channels are differentially expressed in pre- and postglomerular vessels, it was hypothesized that they impact renal blood flow and GFR differentially. The question was addressed with the use of two T-type Cav knockout (Cav3.1(-/-) and Cav3.2(-/-)) mouse strains. Continuous recordings of blood pressure and heart rate, para-aminohippurate clearance (renal plasma flow), and inulin clearance (GFR) were performed in conscious, chronically catheterized, wild-type (WT) and Cav3.1(-/-) and Cav3.2(-/-) mice. The contractility of afferent and efferent arterioles was determined in isolated perfused blood vessels. Efferent arterioles from Cav3.2(-/-) mice constricted significantly more in response to a depolarization compared with WT mice. GFR was increased in Cav3.2(-/-) mice with no significant changes in renal plasma flow, heart rate, and blood pressure. Cav3.1(-/-) mice had a higher renal plasma flow compared with WT mice, whereas GFR was indistinguishable from WT mice. No difference in the concentration response to K(+) was observed in isolated afferent and efferent arterioles from Cav3.1(-/-) mice compared with WT mice. Heart rate was significantly lower in Cav3.1(-/-) mice compared with WT mice with no difference in blood pressure. T-type antagonists significantly inhibited the constriction of human intrarenal arteries in response to a small depolarization. In conclusion, Cav3.2 channels support dilatation of efferent arterioles and affect GFR, whereas Cav3.1 channels in vivo contribute to renal vascular resistance. It is suggested that endothelial and nerve localization of Cav3.2 and Cav3.1, respectively, may account for the observed effects.
authors: Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark;
authors: Anne D
authors: AD
authors: Thuesen
authors: Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark;
authors: Henrik
authors: H
authors: Andersen
authors: Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark;
authors: Majken
authors: M
authors: Cardel
authors: Department of Urology, Odense University Hospital, Odense, Denmark; and.
authors: Anja
authors: A
authors: Toft
authors: Department of Urology, Odense University Hospital, Odense, Denmark; and.
authors: Steen
authors: S
authors: Walter
authors: Clinical Pathology, Odense University Hospital, Odense, Denmark.
authors: Niels
authors: N
authors: Marcussen
authors: Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark;
authors: Boye L
authors: BL
authors: Jensen
authors: Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark;
authors: Peter
authors: P
authors: Bie
authors: Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark; pbhansen@health.sdu.dk.
authors: Pernille B L
authors: PB
authors: Hansen
mesh_terms: D000818:Animals; D001160:Arterioles / Q000187:drug effects; D020747:Calcium Channels, T-Type / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006801:Humans; D007444:Inulin; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012079:Renal Circulation / Q000502:physiology*; D017595:Renal Plasma Flow / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D010130:p-Aminohippuric Acid
chemical_list: C498197:Cacna1g protein, mouse; C504883:Cacna1h protein, mouse; D020747:Calcium Channels, T-Type; D007444:Inulin; D010130:p-Aminohippuric Acid
keywords: afferent arteriole; efferent arteriole; kidney arteries