Differential effect of T-type voltage-gated Ca2+ channel disruption on renal plasma flow and glomerular filtration rate in vivo

Autor: Pernille Lund Hansen, Anne D Thuesen, Majken Cardel, Henrik J. Andersen, Anja Toft, Peter Bie, Boye L. Jensen, Niels Marcussen, Walter S
Rok vydání: 2014
Předmět:
Zdroj: Thuesen, A D, Andersen, H, Cardel, M, Toft, A, Walter, S, Marcussen, N, Jensen, B L, Bie, P & Hansen, P B L 2014, ' Differential effect of T-type voltage-gated Ca 2+ channel disruption on renal plasma flow and glomerular filtration rate in vivo ', American Journal of Physiology: Renal Physiology, vol. 307, no. 4, pp. F445-F452 . https://doi.org/10.1152/ajprenal.00016.2014
ISSN: 1522-1466
1931-857X
Popis: Voltage-gated Ca2+ (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.
Databáze: OpenAIRE