EFFECT OF CELIPROLOL THERAPY ON ARTERIAL DILATATION IN EXPERIMENTAL-HYPERTENSION

1 It has recently been suggested that therapy with beta-adrenoceptor b lockers reduces peripheral arterial resistance via enhanced vascular d ilatation. Therefore, we studied the effects of celiprolol, which is a specific beta(1)-antagonist that has a weak beta(2)-agonist action, o n arterial tone in spontaneously hypertensive rats (SHR) and Wistar-Ky oto (WKY) rats. 2 Two doses of celiprolol (5 and 50 mg kg(-1) day(-1)) were administered to the SHR, while the WKY rats received only the hi gher dose of the drug. During the 12-week treatment period the higher dose attenuated the increase in blood pressure by approximately 20 mmH g in SHR, whereas the lower dose was without significant antihypertens ive effect. Celiprolol therapy did not affect blood pressure in the no rmotensive WKY rats. 3 Responses of mesenteric arterial rings in vitro were examined at the end of the study. Interestingly, endothelium-med iated relaxations of noradrenaline (NA)-precontracted rings to acetylc holine (ACh) in the absence and presence of the cyclo-oxygenase inhibi tor, diclofenac, were equally enhanced in both celiprolol-treated SHR groups. The nitric oxide synthase inhibitor N-G-nitro-L-arginine methy l ester (L-NAME) practically abolished the relaxations to ACh in all S HR irrespective of whether they had received celiprolol, whereas in WK Y rats L-NAME only attenuated the responses to ACh. However, no differ ences were found between the SHR groups in relaxations to ACh when hyp erpolarization of smooth muscle was prevented by precontractions induc ed by 50 mM KCI. Vasorelaxation of NA-precontracted rings to the exoge nous nitric oxide donor, nitroprusside, was also moderately augmented in both celiprolol-treated SHR groups, while the relaxation to beta-ad renoceptor agonist, isoprenaline, remained equally impaired in all SHR whether or not they had received celiprolol. No differences were obse rved between the two WKY groups in the responses to ACh, nitroprusside or isoprenaline. 4 Contractile sensitivity of mesenteric arterial rin gs to the receptor-mediated agonists, NA and 5-hydroxytryptamine, was comparable in all study groups. 5 In conclusion, SHR treatment with ei ther the low or the higher dose of celiprolol was accompanied by enhan cement of both endothelium-dependent and endothelium-independent nitri c oxide-mediated arterial relaxation, possibly via a hyperpolarization mechanism. Interestingly, this effect appeared to be independent of t he reduction in blood pressure.