Simvastatin and Losartan Enhance Nitric Oxide and Reduce Oxidative Stress in Salt-Induced Hypertension

• Published in: American journal of hypertension Vol. 18; no. 11; pp. 1496 - 1502
• Main Authors: Bayorh, Mohamed A., Ganafa, Agaba A., Eatman, Danita, Walton, Marcus, Feuerstein, Giora Z.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.11.2005; Oxford University Press; Elsevier Science
• Subjects: Acetylcholine - pharmacology; aldosterone; Aldosterone - blood; Aldosterone - metabolism; angiotensin II; Angiotensin II - blood; Angiotensin II - metabolism; Angiotensin II Type 1 Receptor Blockers - administration & dosage; Angiotensin II Type 1 Receptor Blockers - therapeutic use; Animals; Aorta - drug effects; Aorta - metabolism; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure - drug effects; Body Weight - drug effects; Cardiology. Vascular system; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Dahl rat; Drug Therapy, Combination; Experimental diseases; Heart Rate - drug effects; Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Hypertension - blood; Hypertension - chemically induced; Hypertension - prevention & control; In Vitro Techniques; Kidney - drug effects; Kidney - metabolism; Kidney - pathology; Losartan - administration & dosage; Losartan - therapeutic use; Male; Medical sciences; Mesenteric Arteries - drug effects; Mesenteric Arteries - physiopathology; Myocardium - metabolism; Myocardium - pathology; nitric oxide; Nitric Oxide - blood; Organ Size - drug effects; Oxidative Stress - drug effects; prostaglandins; Prostaglandins - blood; Rats; Rats, Inbred Dahl; salt-sensitive hypertension; Simvastatin - administration & dosage; Simvastatin - therapeutic use; Sodium Chloride, Dietary - administration & dosage; superoxide; Superoxides - metabolism; Thromboxane A2 - blood; Treatment Outcome; Vasoconstriction - drug effects; Vasodilator Agents - pharmacology; Dahl rat; nitric oxide; angiotensin II; aldosterone; salt-sensitive hypertension; prostaglandins; superoxide; Oxidative stress; Tetrazole derivatives; Rat; Mineralocorticoid; Peptide hormone; Non peptide compound; Cardiovascular disease; Aldosterone; Octapeptide; Losartan; Angiotensin II; Hypertension; Prostaglandin; Enzyme; Steroid hormone; Simvastatin; Rodentia; Enzyme inhibitor; Statin derivative; AT1 angiotensin receptor; Vertebrata; Hyperoxides; Mammalia; Biphenyl derivatives; Animal; Nitric oxide; Adrenal hormone; Hydroxymethylglutaryl-CoA reductase; Antihypertensive agent; Angiotensin antagonist; Oxidoreductases; Antilipemic agent
• ISSN: 0895-7061; 1879-1905; 1941-7225
• DOI: 10.1016/j.amjhyper.2005.05.022

The renin-angiotensin-aldosterone system and oxidative stress play a major role in the pathogenesis of hypertension. We examined the effects of simvastatin, an HMG-CoA inhibitor, and losartan, an angiotensin type 1 receptor antagonist, in Dahl rats fed a high salt diet (8% NaCl), and treated with either simvastatin (3 mg/kg/d), losartan (10 mg/kg/d), or their combination using the drinking water as vehicle, for 3 weeks. Mean blood pressure (MAP) was measured by tail–cuff plethysmography. Plasma levels of nitric oxide (NO) and prostanoids, as well as plasma and tissue angiotensin II (Ang II) and aldosterone (ALDO) were analyzed by enzyme immunoassay. Renal and aortic superoxide production was determined by fluorescence spectrometry. Vascular reactivity of second-order mesenteric arteries was assessed in vitro. Simvastatin, losartan, and the drug combination attenuated the salt-induced increase in MAP. Plasma NO was elevated by simvastatin, losartan, and the combination, whereas plasma thromboxane was reduced by losartan. Simvastatin, losartan, and the combination reduced renal Ang II, but only the combination reduced cardiac Ang II. Heart and renal ALDO were reduced by simvastatin, losartan, and the combination. Aortic and renal NADPH-dependent superoxide production was reduced by simvastatin, losartan, and the combination. The response to acetylcholine, in mesenteric arteries preconstricted with norepinephrine, was greater in the losartan group. Thus, treatment with simvastatin and losartan lowered oxidative stress and improved endothelial function. Simvastatin significantly reduced the effect of losartan on vascular reactivity in mesenteric arteries, suggesting that their combination may be contraindicated.