(Hypertension. 1996;28:797-805.)
© 1996 American Heart Association, Inc.
Articles |
Intracellular Ca2+ Modulation by Angiotensin II and Endothelin-1 in Cardiomyocytes and Fibroblasts From Hypertrophied Hearts of Spontaneously Hypertensive Rats
the Medical Research Council (MRC) Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, University of Montreal (Quebec, Canada).
The vasoactive peptides angiotensin II (Ang II) and endothelin-1 (ET-1) have been implicated in cardiac hypertrophy. This study investigates Ang II and ET-1 effects on intracellular free calcium concentration and the receptor subtype through which agonist-induced calcium responses are mediated in isolated cardiomyocytes and fibroblasts from hypertrophied hearts of spontaneously hypertensive rats (SHR). We measured intracellular free calcium concentration by fura 2 methodology and determined receptor status by radioligand binding assays. Ang II (10-12 to 10-7 mol/L) had no effect on cardiomyocyte calcium levels in control Wistar-Kyoto rats but significantly increased (P<.01) intracellular free calcium concentration in a dose-dependent manner in cardiomyocytes from SHR. Ang II total and specific binding were increased (P<.05) in SHR cardiomyocytes. Calcium responses elicited by 10-7 to 10-5 mol/L Ang II were significantly reduced (P<.01) in SHR fibroblasts despite no significant change in Ang II receptor density. The angiotensin type 1 receptor blocker losartan (1 µmol/L) blocked Ang II–stimulated calcium transients, whereas the angiotensin type 2 receptor blocker PD 123319 had no effect. ET-1– and sarafotoxin S6c–induced calcium responses in cardiomyocytes and fibroblasts were not different between hypertensive and control groups. In conclusion, Ang II and ET-1 elicit distinct and differential responses in a cell-specific manner in cardiomyocytes and fibroblasts from hypertrophied hearts of SHR. Whereas Ang II–mediated effects, which are elicited via angiotensin type 1 receptors, are detectable in cardiomyocytes from SHR, responses to Ang II are blunted in fibroblasts from SHR, and ET-1–related actions are similar in cells from both rat groups. Stimulation of cardiomyocytes by Ang II in hypertrophied hearts associated with pressure overload in genetic hypertension suggests that Ang II could modulate the function of cardiomyocytes of SHR but not those of Wistar-Kyoto rats, whereas cardiac actions of ET-1 do not change with the development of hypertension.
Key Words: rats, inbred SHR • hypertrophy • angiotensin II • endothelin • intracellular • receptors, angiotensin
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