?-Adrenoceptor subtypes in rat aorta and mesenteric small arteries are preserved during left ventricular dysfunction post-myocardial infarction

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Abstract
Objective: In heart failure, homologous downregulation of β-adrenoceptors contributes to impaired adrenergic responsiveness of the myocardium. We evaluated α1,-adrenoceptors (α1-AR) in a sparsely innervated and a densely innervated peripheral artery in an experimental model of left ventricular dysfunction post-myocardial infarction. Methods: [3H]Prazosin binding was determined in arterial segments of Wistar-Kyoto rats (WKY), and of Wistar rats 5 weeks after myocardial infarction (MI) or sham operation (SHAM). Results: In the thoracic aorta (TAO) of WKY, specific prazosin binding was: (i) prevented by the irreversible α 1 B -AR and relatively selective α1 D -AR antagonist, chloroethylclonidine (CEC); (ii) displaced with low affinity (p K i 6.25) by the α1 A -AR selective ligand, (+)-niguldipine; and (iii) displaced with both high (p K i 10.4) and low (p K i 7.37) affinity by the α1 D -AR antagonist, BMY 7378. In mesenteric small arteries (MSA) of WKY, prazosin binding was: (i) reduced 50% by CEC; (ii) displaced in a biphasic fashion by (+)-niguldipine (p K i 8.60 and p K i 6.22); and (iii) displaced by BMY 7378 with low affinity only (p K i 6.86). Also in TAO of SHAM, prazosin binding was prevented by CEC, but neither 30 nM (+)-niguldipine nor 1 nM BMY 7378 affected it. In MSA of SHAM, prazosin binding was virtually abolished in the presence of 30 nM (+)-niguldipine and was not reduced by 1 nM BMY 7378. In TAO and MSA of MI, compared to SHAM, the density of binding sites tended to be increased rather than decreased and neither the affinity for the ligand nor the effects of α1-AR subtype selective tools were significantly modified. Conclusions: These findings indicate that: (i) radioligand binding can be applied in intact arterial segments to quantify and characterize α1-AR; (ii) although differences seem to exist between rat strains, α1 B -AR and α1D-AR predominate in rat thoracic aorta and α1 A -AR and α1B-AR in mesenteric small arteries; and (iii) α1-AR density is not reduced in the poorly innervated aorta and the densely innervated mesenteric small arteries of rats with heart failure due to myocardial infarction.

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