Humoral effects of selective adenosine agonists in spontaneously hypertensive rats.
OBJECTIVE
We studied the dose-response effects of acute administration of the selective A1 adenosine receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA), the selective A2A agonists 2-hexynyl-5'-N-ethylcarboxamidoadenosine (2HE-NECA) and 2-[4-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamidoadenosine (CGS 21680) and the non-selective agonist N-ethylcarboxamidoadenosine (NECA) on plasma renin activity, atrial natriuretic peptide, cyclic guanosine 3',5'-monophosphate (cGMP) and endothelin-1 in spontaneously hypertensive rats.


METHODS
The drugs were administered intraperitoneally in four doses to conscious rats. Systolic blood pressure and heart rate were measured by the tail-cuff technique. Both humoral and hemodynamic parameters were determined 1 h after dosing in separate sets of animals.


RESULTS
All the compounds induced a dose-dependent decrease in systolic blood pressure that was associated with different changes in heart rate. Heart rate was decreased by all doses of CCPA and by the higher doses of the non-selective compound (NECA) and increased by both A2A agonists. Plasma renin activity also changed in opposite directions, being decreased by CCPA but increased dose-dependently by 2HE-NECA and CGS 21680 and only moderately by NECA. Plasma atrial natriuretic peptide and cGMP levels increased dose-dependently after CCPA and NECA, but were unaffected by the A2A agonists. None of the compounds altered plasma endothelin-1 levels.


CONCLUSIONS
These results indicate that the renin-suppressive effect of the A1 agonist, which is associated with a cardiodepressant action, may be attributed either to a direct inhibition of renin release or to the concomitant increments in plasma atrial natriuretic peptide and its second messenger, cGMP. In contrast, the renin-stimulating effect of the A2A agonists may result either from direct stimulation of renin secretion or from reflex sympathetic activation secondary to the fall in blood pressure.
Sala
C
C
Istituto di Clinica Medica Generale e Terapia Medica and Centro Fisiologia Clinica e Ipertensione, Università and Ospedale Maggiore, Milan, Italy.
Monopoli
A
A
Alberti
C
C
Casati
C
C
Ongini
E
E
Zanchetti
A
A
Morganti
A
A
D000241:Adenosine / Q000008:administration & dosage* / Q000819:agonists*; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000008:administration & dosage / Q000819:agonists / Q000031:analogs & derivatives*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000819:agonists*; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000097:blood; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000097:blood / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008955:Models, Cardiovascular; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D011918:Rats, Inbred SHR; D012083:Renin / Q000097:blood / Q000187:drug effects
D000959:Antihypertensive Agents; D019332:Endothelin-1; D058906:Purinergic P1 Receptor Agonists; C076864:2-hexynyladenosine-5'-N-ethylcarboxamide; D019830:Adenosine-5'-(N-ethylcarboxamide); D009320:Atrial Natriuretic Factor; D012083:Renin; D006152:Cyclic GMP; D000241:Adenosine