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

Kähönen, Mika; Mäkynen, Heikki; Arvola, Pertti; Pörsti, Ilkka

doi:10.1111/j.1476-5381.1994.tb13169.x

Cited by 12 publications

(4 citation statements)

References 42 publications

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“…More recently, an increase in nitric oxide (NO) synthesis, a decrease in superoxide anion generation and anti‐oxidant properties 13–15 have been proposed as possible mechanisms of the antihypertensive effects of beta‐blockers. However, endothelial NO‐independent mechanisms also seem to contribute to the therapeutic effects of beta‐blockers, including increased generation of vasodilator prostaglandin by the kidney and vessels, reduced release of endothelium‐derived contractile factors, improvement of the vascular Na + /K + ‐ATPase and enhancement in the ability of vascular smooth muscle to sequester calcium (Ca 2+ ) into cellular stores 16–18 …”

Section: Introductionmentioning

confidence: 99%

Vasorelaxing Effects of Propranolol in Rat Aorta and Mesenteric Artery: A Role for Nitric Oxide and Calcium Entry Blockade

Priviero

Teixeira

Toque

et al. 2006

Clin Exp Pharma Physio

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1. Propranolol has been prescribed successfully to patients with cardiovascular diseases, but the exact mechanisms by which it reduces peripheral vascular resistance have been poorly investigated. 2. The present study was designed to investigate the relaxing effects of propranolol in the rat isolated aorta and mesenteric artery, focusing on the contribution of the nitric oxide (NO)-cGMP pathway and calcium entry blockade. Relaxation responses to propranolol were obtained in precontracted rat aortic and mesenteric artery rings. 3. DL-Propranolol (10-100 micromol/L) produced concentration-dependent relaxations in the aorta and mesenteric artery rings with intact endothelium. The isomers D- and L-propranolol produced relaxation responses that were equipotent to the racemic mixture. 4. Metoprolol (10-100 micromol/L) produced slight relaxations, whereas atenolol (10-100 micromol/L) had no relaxant activity. 5. The NO inhibitor N(G)-nitro-L-arginine methyl ester (100 micromol/L) and the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (1 micromol/L), as well as removal of the endothelium, significantly reduced the relaxation responses induced by the lower concentrations of propranolol without affecting maximal responses. In addition, DL-propranolol markedly increased cGMP levels in endothelium-intact preparations. 6. In Ca(2+)-free Krebs' solution, DL-propranolol (10-100 micromol/L) caused marked rightward shift in the concentration-response curves to CaCl(2), with a decrease of maximal responses in tissues with either intact or denuded endothelium. Nifedipine (1 micromol/L) in combination with DL-propranolol virtually abolished the CaCl(2)-induced contractile responses. 7. The relaxation responses induced by DL-propranolol were significantly reduced in aortic and mesenteric rings precontracted with phorbol-12,13-dibutyrate (1 micromol/L). 8. In conclusion, DL-propranolol relaxes arterial smooth muscle by mechanisms involving activation of the NO-cGMP pathway and calcium influx blockade, independent of beta-adrenoceptor blockade.

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Section: Introductionmentioning

confidence: 99%

Vasorelaxing Effects of Propranolol in Rat Aorta and Mesenteric Artery: A Role for Nitric Oxide and Calcium Entry Blockade

Priviero

Teixeira

Toque

et al. 2006

Clin Exp Pharma Physio

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“…The concentration of celiprolol in the drinking water was weekly adjusted to the drinking habits of the animals. These daily doses of the drug were chosen on the basis of our previous experience of fl-adrenoceptor antagonism with atenolol in SHR (Kahonen et al, 1994). Thus, 50 mg kg-1 day-' of celiprolol was intended to lower blood pressure significantly in SHR, while 5 mg kg-' day-' was not expected to affect it.…”

Section: Animals and Experimental Designmentioning

confidence: 99%

Effect of celiprolol therapy on arterial dilatation in experimental hypertension

Tolvanen¹,

Wu²,

Kähönen

et al. 1996

British J Pharmacology

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1 It has recently been suggested that therapy with ,B-adrenoceptor blockers reduces peripheral arterial resistance via enhanced vascular dilatation. Therefore, we studied the effects of celiprolol, which is a specific l,-antagonist that has a weak fl2-agonist action, on arterial tone in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. 2 Two doses of celiprolol (5 and 50 mg kg-' day-') were administered to the SHR, while the WKY rats received only the higher dose of the drug. During the 12-week treatment period the higher dose attenuated the increase in blood pressure by approximately 20 mmHg in SHR, whereas the lower dose was without significant antihypertensive effect. Celiprolol therapy did not affect blood pressure in the normotensive WKY rats. 3 Responses of mesenteric arterial rings in vitro were examined at the end of the study. Interestingly, endothelium-mediated relaxations of noradrenaline (NA)-precontracted rings to acetylcholine (ACh) in the absence and presence of the cyclo-oxygenase inhibitor, diclofenac, were equally enhanced in both celiprolol-treated SHR groups. The nitric oxide synthase inhibitor N6-nitro-L-arginine methyl ester (L-NAME) practically abolished the relaxations to ACh in all SHR irrespective of whether they had received celiprolol, whereas in WKY rats L-NAME only attenuated the responses to ACh. However, no differences were found between the SHR groups in relaxations to ACh when hyperpolarization of smooth muscle was prevented by precontractions induced by 50 mM KC1. Vasorelaxation of NAprecontracted rings to the exogenous nitric oxide donor, nitroprusside, was also moderately augmented in both celiprolol-treated SHR groups, while the relaxation to ,B-adrenoceptor agonist, isoprenaline, remained equally impaired in all SHR whether or not they had received celiprolol. No differences were observed between the two WKY groups in the responses to ACh, nitroprusside or isoprenaline. 4 Contractile sensitivity of mesenteric arterial rings to the receptor-mediated agonists, NA and 5-hydroxytryptamine, was comparable in all study groups. 5 In conclusion, SHR treatment with either the low or the higher dose of celiprolol was accompanied by enhancement of both endothelium-dependent and endothelium-independent nitric oxide-mediated arterial relaxation, possibly via a hyperpolarization mechanism. Interestingly, this effect appeared to be independent of the reduction in blood pressure.

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“…, 1989). Blood pressure control by atenolol seems to happen through regulation of vascular tone, which leads to vasodilatation in resistance vessels (Man in't Veld & Schalekamp, 1983a), improvement of arterial relaxation and normalization of endothelial function (Kahonen, Makynen, Arvola & Porsti, 1994). Atenolol interference with vascular morphology occurs at two different levels: (1) atenolol prevents the blood pressure rise and consequently, should prevent the cardiovascular remodelling dependent on blood pressure elevation; and (2) atenolol can induce hypertrophy by itself.…”

Section: Discussionmentioning

confidence: 99%

Losartan and atenolol on hypertension induced by adenosine receptor blockade

Morato

Sousa

Guimarães

et al. 2003

Auton Autocoid Pharmacol

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1. The prolonged infusion of 1,3-dipropyl-8-sulfophenylxanthine (DPSPX), a non-selective antagonist of adenosine receptors, induces hypertension, an increase in plasma renin activity and morphological cardiovascular changes. 2. The aim of this work was to evaluate the effects of losartan, a selective AT1 receptor antagonist, and atenolol, a beta-adrenoceptor antagonist, on DPSPX-induced hypertension. 3. Male Wistar rats (250-300 g, n = 4-6) were treated for 1 or 4 weeks with: saline i.p.; DPSPX (90 microg kg(-1) h(-1)) i.p.; losartan (15 mg kg(-1) day(-1)) p.o.; atenolol (25 mg kg(-1) day(-1)) p.o.; DPSPX (90 microg kg(-1) h(-1)) i.p. + losartan (15 mg kg(-1) day(-1)) p.o.; DPSPX (90 microg kg(-1) h(-1)) i.p. + atenolol (25 mg kg(-1) day(-1)) p.o. Blood pressure was measured by the 'tail-cuff' method in conscious animals. Fragments of the mesenteric and tail arteries were processed for morphological study and the mean diameter of the vascular smooth muscle cells was determined. 4. DPSPX increased blood pressure. Losartan and atenolol prevented this rise but had no effect on blood pressure of control rats. DPSPX-treated groups showed hypertrophy of the vascular smooth muscle cells and proliferation of subintimal cells. Losartan but not atenolol prevented these changes. Losartan had no effect on the vascular morphology of control rats, while treatment with atenolol for 4 weeks induced hypertrophy of the vascular smooth muscle cells. 5. Both losartan and atenolol counteract the development of DPSPX-induced hypertension but only losartan prevents the alterations in vascular morphology.

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

Cited by 12 publications

References 42 publications

Vasorelaxing Effects of Propranolol in Rat Aorta and Mesenteric Artery: A Role for Nitric Oxide and Calcium Entry Blockade

Vasorelaxing Effects of Propranolol in Rat Aorta and Mesenteric Artery: A Role for Nitric Oxide and Calcium Entry Blockade

Effect of celiprolol therapy on arterial dilatation in experimental hypertension

Losartan and atenolol on hypertension induced by adenosine receptor blockade

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