Simvastatin upregulates coronary vascular endothelial nitric oxide production in conscious dogs

Seema Mital, Xiaoping Zhang, Gong Zhao, Robert D. Bernstein, Carolyn J. Smith, David J Fulton, William C. Sessa, James K. Liao, Thomas H. Hintze

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

Statin drugs can upregulate endothelial nitric oxide (NO) synthase (eNOS) in isolated endothelial cells independent of lipid-lowering effects. We investigated the effect of short-term simvastatin administration on coronary vascular eNOS and NO production in conscious dogs and canine tissues. Mongrel dogs were instrumented under general anesthesia to measure coronary blood flow (CBF). Simvastatin (20 mg · kg-1 · day-1) was administered orally for 2 wk; afterward, resting CBF was found to be higher compared with control (P < 0.05) and veratrine-(activator of reflex cholinergic NO-dependent coronary vasodilation) and ACh-mediated coronary vasodilation were enhanced (P < 0.05). Response to endothelium-independent vasodilators, adenosine and nitroglycerin, was not potentiated. After simvastatin administration, plasma nitrate and nitrite (NO(x)) levels increased from 5.22 ± 1.2 to 7.79 ± 1.3 μM (P < 0.05); baseline and agonist-stimulated NO production in isolated coronary microvessels were augmented (P < 0.05); resting in vivo myocardial oxygen consumption (MV̇O2) decreased from 6.8 ± 0.6 to 5.9 ± 0.4 ml/min (P < 0.05); NO-dependent regulation of MV̇O2 in response to NO agonists was augmented in isolated myocardial segments (P < 0.05); and eNOS protein increased 29% and eNOS mRNA decreased 50% in aortas and coronary vascular endothelium. Short-term administration of simvastatin in dogs increases coronary endothelial NO production to enhance NO-dependent coronary vasodilation and NO-mediated regulation of MV̇O2.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume279
Issue number6 48-6
StatePublished - Dec 1 2000

Fingerprint

Simvastatin
Blood Vessels
Nitric Oxide
Up-Regulation
Dogs
Vasodilation
Veratrine
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Nitric Oxide Synthase Type III
Vascular Endothelium
Nitroglycerin
Nitrites
Microvessels
Vasodilator Agents
Oxygen Consumption
Nitrates
Adenosine
General Anesthesia
Cholinergic Agents
Endothelium

Keywords

  • Coronary vasodilation
  • Myocardial oxygen consumption
  • Statins

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Simvastatin upregulates coronary vascular endothelial nitric oxide production in conscious dogs. / Mital, Seema; Zhang, Xiaoping; Zhao, Gong; Bernstein, Robert D.; Smith, Carolyn J.; Fulton, David J; Sessa, William C.; Liao, James K.; Hintze, Thomas H.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 279, No. 6 48-6, 01.12.2000.

Research output: Contribution to journalArticle

Mital, S, Zhang, X, Zhao, G, Bernstein, RD, Smith, CJ, Fulton, DJ, Sessa, WC, Liao, JK & Hintze, TH 2000, 'Simvastatin upregulates coronary vascular endothelial nitric oxide production in conscious dogs', American Journal of Physiology - Heart and Circulatory Physiology, vol. 279, no. 6 48-6.
Mital, Seema ; Zhang, Xiaoping ; Zhao, Gong ; Bernstein, Robert D. ; Smith, Carolyn J. ; Fulton, David J ; Sessa, William C. ; Liao, James K. ; Hintze, Thomas H. / Simvastatin upregulates coronary vascular endothelial nitric oxide production in conscious dogs. In: American Journal of Physiology - Heart and Circulatory Physiology. 2000 ; Vol. 279, No. 6 48-6.
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AU - Fulton, David J

AU - Sessa, William C.

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AU - Hintze, Thomas H.

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