Sodium nitrite exerts an antihypertensive effect and improves endothelial function through activation of eNOS in the SHR.
Sodium nitrite (NaNO2) induces relaxation in isolated arteries partly through an endothelium-dependent mechanism involving NO-eNOS-sGC-cGMP pathway. The present study was designed to investigate the effect of chronic NaNO2 administration on arterial systolic blood pressure (SBP) and vascular function in hypertensive rats. NaNO2 (150 mg L-1) was given in drinking water for four weeks to spontaneously (SHR) and Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) treated hypertensive SD rats. Arterial SBP and vascular function in isolated aortae were studied. Total plasma nitrate/nitrite and vascular cyclic guanosine monophosphate (cGMP) levels were measured using commercially available assay kits. Vascular nitric oxide (NO) levels were evaluated by DAF-FM fluorescence while the proteins involved in endothelial nitric oxide synthase (eNOS) activation was determined by Western blotting. NaNO2 treatment reduced SBP, improved the impaired endothelium-dependent relaxation, increased plasma total nitrate/nitrite level and vascular tissue NO and cGMP levels in SHR. Furthermore, increased presence of phosphorylated eNOS and Hsp-90 was observed in NaNO2-treated SHR. The beneficial effect of nitrite treatment was not observed in L-NAME treated hypertensive SD rats. The present study provides evidence that chronic treatment of genetically hypertensive rats with NaNO2 improves endothelium-dependent relaxation in addition to its antihypertensive effect, partly through mechanisms involving activation of eNOS.
Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Wei Chih
WC
Ling
Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Dharmani Devi
DD
Murugan
Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Yeh Siang
YS
Lau
Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.|State Key Laboratory for Pharmaceutical Biotechnology, Department of Pharmacology and Pharmacy and University of Hong Kong, Hong Kong, China.
Paul M
PM
Vanhoutte
Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Mohd Rais
MR
Mustafa
D000109:Acetylcholine / Q000008:administration & dosage; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism*; D062186:Arterial Pressure; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular; D004789:Enzyme Activation / Q000187:drug effects; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006973:Hypertension / Q000503:physiopathology* / Q000517:prevention & control; D008297:Male; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D010766:Phosphorylation; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D012977:Sodium Nitrite / Q000008:administration & dosage*
D000959:Antihypertensive Agents; D018841:HSP90 Heat-Shock Proteins; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D006152:Cyclic GMP; D012977:Sodium Nitrite; D000109:Acetylcholine