November 1, 1996Hypertension43 citations
Intracellular Ca2+Modulation by Angiotensin II and Endothelin-1 in Cardiomyocytes and Fibroblasts From Hypertrophied Hearts of Spontaneously Hypertensive Rats
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Key Result
Angiotensin II significantly increased intracellular free calcium concentration in cardiomyocytes from spontaneously hypertensive rats (P<0.01) but had no effect in control Wistar-Kyoto rats.
Structured PICO
Does Ang II and ET-1 modulate intracellular calcium differently in cardiomyocytes and fibroblasts from hypertrophied hearts of spontaneously hypertensive rats compared to controls?
P
Population
Isolated cardiomyocytes and fibroblasts from hypertrophied hearts of spontaneously hypertensive rats (SHR) and control Wistar-Kyoto rats
I
Intervention
Angiotensin II (10(-12) to 10(-5) mol/L) and endothelin-1
C
Comparator
Cells from control Wistar-Kyoto rats
O
Outcome
Intracellular free calcium concentration (measured by fura 2 methodology) and receptor status (determined by radioligand binding assays)surrogate
Angiotensin II elicits distinct, cell-specific calcium responses via AT1 receptors in cardiomyocytes from spontaneously hypertensive rats, suggesting a modulatory role in hypertrophy associated with genetic hypertension.
Main Result
p-value: p=<0.01
Abstract
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 mumol/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.
Cite This Study
Touyz et al. (1996) studied Cardiac hypertrophy and hypertension. Angiotensin II and Endothelin-1 vs. Control Wistar-Kyoto rats was evaluated on Intracellular free calcium concentration (p=<0.01). Angiotensin II significantly increased intracellular free calcium concentration in cardiomyocytes from spontaneously hypertensive rats (P<0.01) but had no effect in control Wistar-Kyoto rats.