HUMORAL EFFECTS OF SELECTIVE ADENOSINE AGONISTS IN SPONTANEOUSLY HYPERTENSIVE RATS

Objective We studied the dose-response effects of acute administration of the selective A(1) adenosine receptor agonist 2-chloro-NG-cyclopen tyladenosine (CCPA), the selective A(2A) agonists 2-hexynyl-5'-N-ethyl carboxamidoadenosine (2HE-NECA) and hyl)phenethylamino]-5'-N-ethylcarb oxamidoadenosine (CGS 21680) and the non-selective agonist N-ethylcarb oxamidoadenosine (NECA) on plasma renin activity, atrial natriuretic p eptide, cyclic guanosine 3',5'-monophospfrate (cGMP) and endothelin-l in spontaneously hypertensive rats. Methods The drugs were administere d intraperitoneally in four doses to conscious rats, Systolic blood pr essure and heart: rate were measured by the tail-cuff technique. Both humoral and hemodynamic parameters were determined Ih after dosing in separate sets of animals. Results All the compounds induced a dose-dep endent decrease in systolic blood pressure that was associated with di fferent changes in heart rate, Heart rate was decreased by all doses o f CCPA and by the higher doses of the non-selective compound (NECA) an d increased by both AZA agonists, Plasma renin activity also changed i n opposite directions, being decreased by CCPA increased dose-dependen tly 2HE-NECA and 21680 and only moderately natriuretic peptide and cGM P levels increased dose-dependently after CCPA and NECA, but were unaf fected by the A(2A) agonists. None of the compounds altered plasma end othelin-1 levels. Conclusions These results indicate that the renin-su ppressive effect of the A(1) agonist, which is associated with a cardi odepressant action, may be attributed either to a direct inhibition of renin release or to the concomitant increments in plasma atrial natri uretic peptide and its second messenger, cGMP. In contrast, the renin- stimulating effect of the A(2A) agonists may result either from direct stimulation of renin secretion or from reflex sympathetic activation secondary to the fall in blood pressure.