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Possible role of exogenous cAMP to improve vascular endothelial dysfunction in hypertensive rats
Author(s) -
Shah Dhvanit I.,
Singh Manjeet
Publication year - 2006
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.2006.00449.x
Subject(s) - p22phox , enos , endothelial dysfunction , medicine , endocrinology , superoxide , oxidative stress , nadph oxidase , tbars , chemistry , nitric oxide , nitric oxide synthase , endothelium , vasoprotective , biochemistry , enzyme , lipid peroxidation
The study has been designed to investigate the effect of 8‐Br‐cAMP, an activator of protein kinase A, in hypertension‐induced vascular endothelial dysfunction. Rats were uninephroctomized and desoxycortisone acetate (DOCA) (40 mg/kg, s.c.) was administered to rats to produce hypertension (mean arterial blood pressure > 140 mmHg). Vascular endothelial dysfunction was assessed using isolated aortic ring preparation, electron microscopy of thoracic aorta and serum concentration of nitrite/nitrate. The expression of mRNA for p22phox and eNOS was assessed by using reverse transcriptase‐polymerase chain reaction. Serum thiobarbituric acid reactive substances concentration and aortic superoxide anion concentration were estimated to assess oxidative stress. 8‐Br‐cAMP (5 mg/kg, i.p.) or atorvastatin (30 mg/kg, p.o.) prevented hypertension‐induced attenuation of acetylcholine‐induced endothelium‐dependent relaxation, impairment of vascular endothelial lining, decrease in expression of mRNA for endothelial nitric oxide synthase (eNOS), serum nitrite/nitrate concentration and increase in expression of mRNA for p22phox, superoxide anion and serum TBARS. The ameliorative effect of 8‐Br‐cAMP was prevented by N ‐nitro‐ l ‐arginine methyl ester (25 mg/kg, i.p.) and glibenclamide (30 mg/kg, i.p.). It may be concluded that 8‐Br‐cAMP may stimulate expression and activity of eNOS and suppress expression of p22phox subunit of NADPH oxidase to reduce oxidative stress and subsequently improve vascular endothelial dysfunction.