Altered sodium-calcium exchange in afferent arterioles of the spontaneously hypertensive rat

Studies were performed to determine if there is a derangement in Na-Ca exchange activity in afferent (AA) and efferent (EA) arterioles from 3- and 9-week-old spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Cytosolic calcium concentration ([Ca2+](i)) was assessed using microscope-based photometry in fura-2 loaded arterioles bathed in a Ringer's solution. Baseline [Ca2+](i) was similar in the AA of 3- and 9-week-old WKY and SHR. In AA from 3-week-old rats, [Ca2+](i) increased by 89 +/- 15 nM in WKY and by 73 +/- 13 nM in SHR during decreases in bath sodium concentration ([Na+](c)) from 150 to 2 mM (Na+ replaced with n-methyl-D-glucamine). In 9-week-old hypertensive SHR (SEP = 150 mm Hg), increases in [Ca2+](i) were attenuated (24 +/- 3 nM) relative to 3-week-old WKY and SHR, and 9-week-old WKY (90 +/- 9 nM; P < 0.05). Likewise, the rate of removal of Ca2+ in the continued presence of 2 mM Na-c (Ca2+ sequestration and/or extrusion) was markedly reduced in AA of 9-week-old SHR (-0.15 +/- 0.03 nM/second) versus 3-week-old SHR (-0.72 +/- 0.12 nM/second) and 3- and 9-week-old WKY (-0.49 +/- 0.10 and -0.67 +/- 0.14 nM/second). In other experiments, AAs were preincubated in 1 mM ouabain to increase intracellular [Na+]. This maneuver augmented the increase in [Ca2+](i) obtained with removal of Na-c(+); however, the responses obtained in 9-week-old SHR arterioles were still attenuated compared to those obtained in arterioles for 3- and 9-week-old WKY and 3-week-old SHR These results suggest that exchanger number and/or sensitivity to the transmembrane Na gradient was reduced in the SHR AA. In EA, baseline [Ca2+](i) was similar in 3- and 9-week-old WKY and SHR. In contrast to AG the magnitude of Na-dependent and Na-independent changes in [Ca2+](i) was not different in the EA of 3- and 9-week-old WKY and SHR. These results indicate that regulation of Na-Ca exchange activity may differ between AA and EA segments. Furthermore, diminished Na-Ca exchange and Na-independent Ca2+ sequestering/extrusion mechanisms could contribute to altered AA [Ca2+](i) in the SHR.