ENHANCEMENT OF ARTERIAL RELAXATION BY LONG-TERM ATENOLOL TREATMENT INSPONTANEOUSLY HYPERTENSIVE RATS

1 The effects of long-term atenolol (25 mg kg(-1) day(-1)) therapy on arterial function were studied in spontaneously hypertensive rats (SHR ) and Wistar-Kyoto (WKY) rats. The 14-week treatment attenuated the in crease in blood pressure by approximately 30 mmHg in SHR, but did not affect blood pressure in WKY rats. 2 Responses of mesenteric arterial rings in vitro were examined at the end of the study. The relaxation t o acetylcholine was similar in WKY rats and atenolol-treated SHR and m ore pronounced than in untreated SHR, whereas the relaxation to the ni tric oxide donor 3-morpholinosydnonimine (SIN-1) was comparable in all study groups. Moreover, after maximal relaxations to acetylcholine, m arked recontractions developed in untreated SHR but not in the other g roups. Vasorelaxation to isoprenaline was also attenuated in SHR and w as moderately improved by the atenolol therapy. 3 Arterial relaxation induced by return of potassium to the organ bath upon precontractions elicited by potassium-free solution were used to evaluate vascular smo oth muscle Na+,K+-ATPase, The rate of potassium relaxation was fastest in WKY rats and was also faster in atenolol-treated than in untreated SHR. 4 The ability of vascular smooth muscle to sequester calcium was evaluated by eliciting responses to caffeine or noradrenaline after l oading periods in different organ bath calcium concentrations. The sub sequent contractions were lower in untreated SHR than in WKY rats, and augmented in SHR by the atenolol treatment. 5 Smooth muscle contracti ons to noradrenaline were comparable in SHR and WKY rats, while atenol ol treatment slightly increased the maximal response to this agonist i n SHR, Responses to potassium chloride were not affected by atenolol a nd contractions following cumulative re-addition of calcium to the org an bath after precontraction with potassium chloride and noradrenaline in calcium-free solution were comparable in all study groups. 6 In co nclusion, the moderate antihypertensive effect of atenolol in SHR was accompanied by enhancement of beta-adrenoceptor-mediated and normaliza tion of endothelium-dependent arterial relaxation. Furthermore, abilit y to sequester calcium into cellular stores, and function of Na+,K+-AT Pase were augmented in vascular smooth muscle. Therefore, the present results suggest that the long-term blood pressure-lowering action of a tenolol in this type of genetic hypertension is accompanied by improve d arterial relaxation and normalization of endothelial function.