Effects of antihypertensive agents on endothelium-dependent and endothelium-independent relaxations.
1. Antihypertensive agents normalize blood pressure and restore depressed endothelium-dependent relaxations in experimental models of hypertension, but little is known regarding whether antihypertensive agents themselves can directly modulate responses to agonists of endothelium-dependent or independent relaxations, or contractions. 2. Normal rats were treated with either tap water, captopril, hydralazine or enalapril in their drinking water for 2 weeks, following which endothelium-dependent and endothelium-independent relaxations were tested with acetylcholine and sodium nitroprusside, respectively, in aortic rings suspended in organ chambers. 3. All antihypertensive agents caused slight but similar potentiation of sodium nitroprusside-induced relaxations. However, their effects on acetylcholine-induced relaxations were quite different: captopril had a marked potentiating effect, hydrazaline a slight potentiating effect, and enalapril had no significant effect on these relaxations. 4. The relaxations induced by acetylcholine and potentiated by captopril were not altered when indomethacin was included in the tissue bath. However, pyrogallol, an inhibitor of endothelium-derived relaxing factor (EDRF), markedly inhibited these relaxations suggesting that captopril's effect may involve EDRF. 5. SQ 14,534, a stereoisomer of captopril which is 100 fold less potent in inhibiting angiotensin converting enzyme, also significantly enhanced acetylcholine induced relaxations. Thus the effects of both captopril and SQ 14,534 upon EDRF appear independent of the effects of these compounds on the angiotensin converting enzyme. 6. We conclude that certain antihypertensive agents may modulate endothelium-dependent relaxations in response to agonists, and that these properties may be of therapeutic importance in cardiovascular diseases.
Shultz
P J
PJ
Department of Medicine, University of Minnesota School of Medicine, Minneapolis.
Raij
L
L
D000109:Acetylcholine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001011:Aorta / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000008:administration & dosage / Q000494:pharmacology; D004656:Enalapril / Q000008:administration & dosage / Q000494:pharmacology; D006830:Hydralazine / Q000008:administration & dosage / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D011748:Pyrogallol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000959:Antihypertensive Agents; D011748:Pyrogallol; D006830:Hydralazine; D009569:Nitric Oxide; D000244:Adenosine Diphosphate; D004656:Enalapril; D002216:Captopril; D000109:Acetylcholine; D007213:Indomethacin