EFFECTS OF AGE ON CA2-ARTERY MYOCYTES FROM WISTAR-KYOTO AND SPONTANEOUSLY HYPERTENSIVE RATS( CURRENTS IN SMALL MESENTERIC)

The purpose of this study was to test the hypothesis that differences in voltage-gated Ca2+ channels increase with age during the developmen t 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) Wis tar-Kyoto rats (WKY) and SHR. Indirect tail artery systolic pressure i ncreased 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 wee ks, 3.5 +/- 0.4 versus 2.3 +/- 0.2 pA/pF; at 12 weeks, 3.8 +/- 0.2 ver sus 3.1 +/- 0.2; at 20 weeks, 4.9 +/- 0.4 versus 3.3 +/- 0.4). Cell ca pacitance (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 wer e found in the 6- or 20-week-old groups. There were significant differ ences in Ca2+ current with strain, age, and voltage but no significant age-strain interactions. The ratio of peak Ca2+ current for SHR to th at of WKY declined linearly with voltage at all ages, suggesting diffe rences in the voltage dependence of Ca2+ current activation. The volta ge 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 ha ve 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 o f these differences predicts a larger Ca2+ current in SHR at voltages in the physiological range of membrane potential.