M. Kahonen et al., ENHANCEMENT OF ARTERIAL RELAXATION BY LONG-TERM ATENOLOL TREATMENT INSPONTANEOUSLY HYPERTENSIVE RATS, British Journal of Pharmacology, 112(3), 1994, pp. 925-933
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.