PURINERGIC ENDOTHELIUM-DEPENDENT AND ENDOTHELIUM-INDEPENDENT CONTRACTIONS IN RAT AORTA

The role of endothelium-derived contracting factor or factors in modul ating relaxations and contractions to adenine nucleotides was examined in aortas from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) and Wistar rats. During contractions to phenylephr ine, the relaxations to ATP were impaired significantly in SHR compare d with WKY aortas with endothelium. In rings treated with N(G)-nitro-L -arginine (to inhibit nitric oxide synthase), the endothelium signific antly augmented contractions evoked by ATP; this enhancement was great er in SHR compared with WKY aortas. Indomethacin (inhibitor of cycloox ygenase) and SQ 29,458 (antagonist of thromboxane/prostaglandin endope roxide receptors) but not dazoxiben (inhibitor of thromboxane synthase ) significantly augmented the maximal relaxation in WKY rats, abolishe d the impairment of the relaxation in SHR, and prevented the potentiat ion by the endothelium of the contractions evoked by ATP. In older ani mals (10 to 12 months old), the endothelium-dependent concentration-re laxation curves to ATP in SHR and WKY aortas treated with indomethacin were superimposable, as were the concentration-contraction curves (wi th N(G)-nitro-L-arginine present). Endothelium-dependent concentration -relaxation and -contraction curves to ADP obtained in these preparati ons overlapped also. In Wistar rats, the magnitude of the endothelium- dependent relaxations to either ATP or ADP were significantly smaller compared with the other strains, and the endothelium-dependent contrac tions were even smaller. Results show that adenine nucleotides stimula te the production of both endothelium-derived relaxing and contracting factors. Although there is no obvious age-related alteration in the c apacity of aortas to release endothelium-derived relaxing factor, agin g enhances endothelium-derived contracting factor activity in WKY rats .