Effects of angiotensin II and angiotensin-(1-7) on the release of [3H]norepinephrine from rat atria.

Abstract

We examined the effects of angiotensin II (Ang II) and Ang-(l-7) on the release of [

Evidence for a functional cardiac interaction between losartan and angiotensin‐(1–7) receptors revealed by orthostatic tilting test in rats

“…Therefore, our study supports previous findings showing that the orthostatic effect caused by losartan is beyond antagonism of Ang II AT 1 receptor blockade (Ohlstein et al, 1992;Hashimoto et al, 1999). Previous reports of nonspecificity of losartan for AT 1 receptors provided arguments to the hypothesis that Ang-(1-7) receptors, in the kidney (Chansel et al, 1994;Gironacci et al, 1999) and perhaps in the heart (Gironacci et al, 1994), are sensitive to losartan. Regarding the latter, a possible interaction at cardiac level is suggested in view of our experiments in which losartan treatment clearly altered the cardiac response normally observed during the control tilt maneuver, causing an accentuated bradycardia.…”

“…The present study adds to growing evidence that suggests the involvement of Ang-(1-7) receptors in cardiac regulation both in normal (Gironacci et al, 1994;Porsti et al, 1994;Brosnihan et al, 1996) or pathological conditions (Ferreira et al, 2001;Loot et al, 2002;Zisman et al, 2003). In addition, our results suggest that losartan might interfere with Ang-(1-7) receptors in the regulation of cardiac chronotropism, which probably accounts for the orthostatic hypotension observed in losartan, but not in candesartan, treated rats.…”

“…Gironacci et al (1994) found that losartan entirely prevented the increases in the electric stimulation-induced release of…”

“…[3H]norepinephrine caused by Ang-(1-7) in the rat atria, suggesting a neuromodulatory and facilitatory action for this heptapeptide on the cardiac sympathetic neurotransmission (Gironacci et al, 1994). In addition, in a model of simulated ventricular ischemia and reperfusion, losartan display antiarrhythmic properties and this activity was independent of AT 1 receptor blockade (Thomas et al, 1996).…”

“…In addition, several previous studies have shown that, under certain conditions, Ang-(1-7) actions can be blocked by relatively low doses of losartan (Santos et al, 2000). Furthermore, reports suggesting a previously unsuspected nonspecificity for losartan provided additional arguments to the hypothesis that Ang-(1-7) receptors, in the kidney (Chansel et al, 1994;Gironacci et al, 1999) and perhaps in the heart (Gironacci et al, 1994), are sensitive to losartan.…”