EFFECTS OF CHRONIC TREATMENT WITH LOSARTAN AND ENALAPRILAT ON [H-3] NOREPINEPHRINE RELEASE FROM ISOLATED ATRIA OF WISTAR-KYOTO AND SPONTANEOUSLY HYPERTENSIVE RATS

The present study was designed to evaluate the effect of chronic treat ment with losartan, an AT(1) angiotensin II receptor antagonist, and e nalaprilat, an angiotensin converting enzyme inhibitor, on the presyna ptic modulation of [H-3]-norepinephrine release from isolated atria of spontaneously hypertensive rats (SHR) and their respective control, t he Wistar-Kyoto rats (WKY). The rats received either losartan (5 mg/kg /day) or enalaprilat (1 mg/kg/day) for 12 days by means of osmotic min ipumps. The atria were isolated and incubated with [H-3]-norepinephrin e and the release of radioactivity was used as an index of norepinephr ine release. The experimental protocol consisted of two electrical sti mulations and the drugs were administered 20 min before the second sti mulation. The modulatory action of angiotensin II (0.01 and 1 mu mol/L ), the alpha(2)-adrenoceptor agonist, oxymetazoline (1 mu mol/L), the alpha(2)-adrenoceptor antagonist, idazoxan (1 mu mol/L) and the beta(2 )-adrenoceptor agonist fenoterol (1 mu mol/L) were tested. The results show that losartan or enalaprilat both similarly reduced the blood pr essure in SHR. However, only the chronic losartan treatment, and not e nalaprilat, abolished the facilitatory effect of exogenously administe red angiotensin II on the release of radioactivity. The prejunctional alpha(2)- and beta(2)-adrenoceptor modulatory mechanisms were not alte red by either chronic treatments, Similarly, the facilitatory effect o f angiotensin II was blocked by acute administration of losartan but n ot by enalaprilat. Finally, the facilitatory action of bradykinin on t he release of radioactivity was unchanged by chronic enalaprilat treat ment. These results confirm the presence of facilitatory AT(1) angiote nsin II receptors on sympathetic nerve terminals of rat atria. These r esults also confirm that sympathetic nerve terminal blockade by losart an or the blockade of endogenous angiotensin II formation by enalapril at are likely to participate in the antihypertensive action of AT(1) a ngiotensin II receptor antagonists and angiotensin converting enzyme.