Enhancement of arterial relaxation by long-term atenolol treatment in spontaneously hypertensive rats

M Kähönen, H Mäkynen, P Arvola, I Pörsti

Research output: Contribution to journalArticleScientificpeer-review

Abstract

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 increase 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 to acetylcholine was similar in WKY rats and atenolol-treated SHR and more pronounced than in untreated SHR, whereas the relaxation to the nitric oxide donor 3-morpholinosydnonimine (SIN-1) was comparable in all study groups. Moreover, after maximal relaxations to acetylcholine, marked recontractions developed in untreated SHR but not in the other groups. Vasorelaxation to isoprenaline was also attenuated in SHR and was 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 smooth 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 loading periods in different organ bath calcium concentrations. The subsequent contractions were lower in untreated SHR than in WKY rats, and augmented in SHR by the atenolol treatment. 5. Smooth muscle contractions to noradrenaline were comparable in SHR and WKY rats, while atenolol treatment slightly increased the maximal response to this agonist in SHR. Responses to potassium chloride were not affected by atenolol and contractions following cumulative re-addition of calcium to the organ bath after precontraction with potassium chloride and noradrenaline in calcium free solution were comparable in all study groups.6. In conclusion, the moderate antihypertensive effect of atenolol in SHR was accompanied by enhancement of beta-adrenoceptor-mediated and normalization of endothelium-dependent arterial relaxation.Furthermore, ability to sequester calcium into cellular stores, and function of Na+,K+-ATPase were augmented in vascular smooth muscle. Therefore, the present results suggest that the long-term blood pressure-lowering action of atenolol in this type of genetic hypertension is accompanied by improved arterial relaxation and normalization of endothelial function.

Original languageEnglish
Pages (from-to)925-933
Number of pages9
JournalBr J Pharmacol
Volume112
Issue number3
DOIs
Publication statusPublished - Jul 1994
Externally publishedYes
Publication typeA1 Journal article-refereed

Keywords

  • Aging/physiology
  • Animals
  • Atenolol/pharmacology
  • Blood Pressure/drug effects
  • Body Weight/drug effects
  • Calcium/metabolism
  • Endothelium, Vascular/physiology
  • Heart Rate/drug effects
  • Hemodynamics/drug effects
  • Hypertension/enzymology
  • In Vitro Techniques
  • Male
  • Mesenteric Arteries/drug effects
  • Muscle Contraction/drug effects
  • Muscle Relaxation/drug effects
  • Muscle, Smooth, Vascular/drug effects
  • Organ Size/drug effects
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Sodium-Potassium-Exchanging ATPase/metabolism

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