Two angiotensin AT1 receptor antagonists, irbesartan and losartan, effects in cholesterol-fed rabbits.
This study was performed to examine the long-term effects of irbesartan and losartan, two angiotensin (AT(1)) receptor antagonists, on lipoproteins and vascular responsiveness in vessels isolated from hypercholesterolemic rabbits. Four groups of rabbits (n=40) were used: Group 0 (control group), Group 1 [hypercholesterolemic group, 0.5% (wt./wt.) cholesterol-enriched diet], Group 2 (hypercholesterolemic+irbesartan 10 mg/kg/day) and Group 3 (hypercholesterolemic+losartan 10 mg/kg/day). After 17 weeks of treatment, total cholesterol and low-density lipoproteins levels in irbesartan- and losartan-treated groups were significantly lower than those of Group 1 (alpha=0.05). Furthermore, levels of high-density lipoproteins were higher in the treated groups than in the hypercholesterolemic (alpha=0.05) when we consider the same level of total cholesterol in the hypercholesterolemic and the treated groups. Despite the effect of the drugs on the abovementioned parameters, treatment with irbesartan or losartan did not improve endothelium-dependent and independent relaxation in aortic and mesenteric rings. Treatment with irbesartan and losartan decreased noradrenaline-induced contraction in aortic rings with respect to that in the hypercholesterolemic group (alpha=0.05). In addition, irbesartan treatment improved the increase in serotonin-induced contraction in proximal coronary arteries with respect to that in the hypercholesterolemic group (alpha=0.05). These results indicate that irbesartan and losartan restore noradrenaline-induced contraction in hypercholesterolemic rabbit-isolated arteries and improve lipoprotein profile in cholesterol-fed rabbits.
Sanz
Mercedes
M
Department of Pharmacology, School of Medicine, Complutense University, Madrid, Spain.
Ganado
Patricia
P
Tejerina
Teresa
T
D000109:Acetylcholine / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001013:Aorta, Thoracic / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002784:Cholesterol / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D003331:Coronary Vessels / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006937:Hypercholesterolemia / Q000209:etiology / Q000503:physiopathology; D066298:In Vitro Techniques; D000077405:Irbesartan; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D044140:Receptor, Angiotensin, Type 1; D012701:Serotonin / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology*; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D002791:Cholesterol, Dietary; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D014665:Vasodilator Agents; D009599:Nitroprusside; D012701:Serotonin; D011189:Potassium Chloride; D002784:Cholesterol; D000077405:Irbesartan; D019808:Losartan; D000109:Acetylcholine; D009638:Norepinephrine