title: Effect of taurine deficiency on adenosine receptor-mediated relaxation of the rat aorta.
abstract: 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.
authors.affiliation: 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
authors.forename: Worku
authors.initials: W
authors.lastname: Abebe
authors.forename: Mahmood S
authors.initials: MS
authors.lastname: Mozaffari
mesh_terms: 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
chemical_list: 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