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(Hypertension. 1997;29:1329-1336.)
© 1997 American Heart Association, Inc.

Articles

Effects of Age on Ca²⁺ Currents in Small Mesenteric Artery Myocytes From Wistar-Kyoto and Spontaneously Hypertensive Rats

Irina M. Lozinskaya; ; Robert H. Cox

From the Bockus Research Institute, The Graduate Hospital, and Department of Physiology, University of Pennsylvania, Philadelphia.

Correspondence to Robert H. Cox, PhD, Bockus Research Institute, The Graduate Hospital, One Graduate Plaza, Philadelphia, PA 19146. E-mail rcox{at}mail.med.upenn.edu

Abstract 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.

Key Words: calcium channels • age • patch-clamp techniques • rats, inbred SHR

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