Effects of age on Ca2+ currents in small mesenteric artery myocytes from Wistar-Kyoto and spontaneously hypertensive rats.

The purpose of this study was to test the hypothesis that differences in voltage-gated Ca2+ channels increase with age during the development of sustained hypertension in the spontaneously hypertensive rat (SHR). Using patch-clamp methods, we measured whole-cell Ca2+ currents in freshly isolated myocytes from small mesenteric arteries of juvenile (5 to 7 weeks), young (10 to 12 weeks), and mature (19 to 23 weeks) Wistar-Kyoto rats (WKY) and SHR. Indirect tail artery systolic pressure increased progressively with age in SHR (from 125 +/- 5 to 159 +/- 5 to 192 +/- 5 mm Hg) but only in the younger WKY (from 107 +/- 6 to 130 +/- 4 to 136 +/- 4 mm Hg). Peak Ca2+ current density (current per cell capacitance) was larger in SHR than WKY myocytes at all ages (at 6 weeks, 3.5 +/- 0.4 versus 2.3 +/- 0.2 pA/pF; at 12 weeks, 3.8 +/- 0.2 versus 3.1 +/- 0.2; at 20 weeks. 4.9 +/- 0.4 versus 3.3 +/- 0.4). Cell capacitance (surface area) was significantly smaller in 12-week-old SHR than WKY (25.2 +/- 1.1 versus 31.8 +/- 1.6 pF), but no differences were found in the 6- or 20-week-old groups. There were significant differences in Ca2+ current with strain, age, and voltage but no significant age-strain interactions. The ratio of peak Ca2+ current for SHR to that of WKY declined linearly with voltage at all ages suggesting differences in the voltage dependence of Ca2+ current activation. The voltage dependence of Ca2+ current was shifted to the left in SHR compared with WKY at all ages. Activation curves were shifted significantly in the negative-voltage direction only in 20-week-old SHR myocytes. We have found differences with age in Ca2+ current density and its voltage dependence in SHR compared with WKY during the phase of development in which blood pressure becomes established in the SHR. The net effect of these differences predicts a larger Ca2+ current in SHR at voltages in the physiological range of membrane potential.

Augmented calcium currents in mesenteric artery branches of the spontaneously hypertensive rat.

The greater efficacy of organic channel blockers in lowering peripheral resistance and blood pressure in hypertensive subjects has been suggested to be the result of augmented calcium influx through L-type calcium channels in arterial smooth muscle. These studies were performed to determine whether differences exist in voltage-gated calcium channels of mesenteric artery branches from 20-week-old spontaneously hypertensive rats (SHR) compared with Wistar-Kyoto rats (WKY). Single myocytes were acutely isolated by collagenase and elastase treatment and studied at room temperature (approximately 20 degrees C) with the use of whole-cell, patch-clamp methods. Maximum values of calcium current measured at 0 mV from a holding potential of -90 mV were larger in SHR myocytes (105 +/- 11 versus 149 +/- 15 pA). Values of cell capacitance were smaller in SHR (29.5 +/- 1.3 pF) compared with WKY (35.0 +/- 1.5 pF) myocytes. Cell capacitance measures surface membrane area and, when used to normalize calcium currents, magnified the difference between WKY and SHR to approximately 47%. There was a larger percent reduction of maximum calcium current at holding potentials of -60 and -40 mV in SHR compared with WKY myocytes: for example, at -40 mV calcium current was reduced from values at -90 mV by -73 +/- 2% in SHR compared with -58 +/- 1% in WKY. When divided by the maximum current for each holding potential, the voltage dependence of normalized calcium currents for the two groups was completely superimposed. Difference currents were calculated by subtracting currents measured from holding potentials of -90 and -40 mV. The voltage dependence of difference currents was identical to that of the calcium currents measured from the two values of holding potential.(ABSTRACT TRUNCATED AT 250 WORDS)