Effect of taurine deficiency on adenosine receptor-mediated relaxation of the rat aorta.
We recently demonstrated that chronic taurine supplementation or deficiency causes alterations in reactivity of the rat aorta to several vasoactive agents. In the present investigation, we examined the effects beta-alanine-induced endogenous taurine deficiency on the mechanical responsiveness of the isolated rat aorta to adenosine receptor stimulation with 2-chloroadenosine (CAD), 5'-N-ethylcarboxyamidoadenosine (NECA), and N(6)-cyclopentyladenosine (CPA). The adenosine analogs produced concentration-dependent (1 x 10(-9)-3 x 10(-3) M) relaxations of aortas from both control and beta-alanine-treated rats with the rank order of potencies NECA>CAD>CPA, which was consistent with A(2) receptor identification. CAD and NECA induced both endothelium-dependent and -independent relaxations of the aortas. The endothelium-dependent responses to both agents and the independent responses to CAD were significantly attenuated by beta-alanine treatment. The relaxation responses of the aortas from control and taurine-deficient rats to CAD and NECA were markedly antagonized by ZM241385 (10(-5) M), suggesting the involvement of A(2A) adenosine receptors. Further, N-nitro-L-arginine methyl ester (L-NAME; 10(-5) M) significantly attenuated the endothelium-mediated relaxation produced by CAD and NECA in both groups. However, the inhibitory effect of L-NAME was less on the beta-alanine-treated tissues, providing evidence that the effect of taurine deficiency was linked to a reduction in nitric oxide generation. As in the aorta, CAD produced both endothelium-dependent and -independent relaxation responses in the rat superior mesenteric artery, and both responses were inhibited by chronic beta-alanine treatment, suggesting that not only similar responses can be generated by a given adenosine agonist in different vascular beds, but also beta-alanine treatment modulates these responses. On the other hand, while CPA elicited only endothelium-independent aortic relaxation, this response was not altered by taurine deficiency. The results indicate that endogenous taurine deficiency causes differential inhibitory effects on adenosine receptor-mediated vasorelaxation, depending upon the agonists used. Given the recognized role of adenosine in the vasculature, these alterations suggest taurine-mediated modulation of blood flow regulation.
Abebe
Worku
W
Department of Oral Biology and Maxillofacial Pathology, School of Dentistry, CB 3710, Medical College of Georgia, Augusta, GA 30912-1128, USA. wabebe@mail.mcg.edu
Mozaffari
Mahmood S
MS
D015762:2-Chloroadenosine / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000502:physiology*; D013654:Taurine / Q000172:deficiency*; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D015091:beta-Alanine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D018047:Receptors, Purinergic P1; D014227:Triazines; D014230:Triazoles; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C097270:ZM 241385; D015091:beta-Alanine; D015762:2-Chloroadenosine; D013654:Taurine; D010656:Phenylephrine; D019830:Adenosine-5'-(N-ethylcarboxamide); C048599:N(6)-cyclopentyladenosine; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D000241:Adenosine; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester