Hypercholesterolemia blunts NO donor-induced late preconditioning against myocardial infarction in conscious rabbits.

Abstract

Although NO donors have been shown to confer late preconditioning (PC) against myocardial ischemia/reperfusion injury in healthy rabbits, it is unknown whether concurrent systemic disorders affect NO donor-induced cardioprotection. Since many patients with coronary artery disease have hypercholesterolemia (HC), we examined the effect of this condition on late PC induced by the NO donor diethylenetriamine/nitric oxide (DETA/ NO). Chronically instrumented rabbits were fed a normal diet (normocholesterolemia, NC) or a diet enriched with 1% cholesterol (HC) for 4 weeks. Plasma cholesterol levels were significantly elevated and the arterial pressure response to the endothelium-dependent vasodilator bradykinin was blunted in cholesterol diet-fed rabbits. Conscious rabbits underwent a 30-minute coronary occlusion followed by 3 days of reperfusion. When NC rabbits were pretreated with DETA/NO (0.1 mg/kg, i. v. x 4, group II, n = 7) 24 hours before the 30-minute occlusion, infarct size was reduced by 52% (29.7 +/- 3.4% versus 62.4 +/- 4.0% of the region at risk in NC controls [group I, n = 5], P < 0.05), indicating that DETA/NO induced a late PC effect against myocardial infarction. In contrast, when HC rabbits were pretreated with the same dose of DETA/NO (group IV, n = 6), infarct size was not significantly reduced (61.0 +/- 5.7% versus 68.1 +/- 4.5% of the region at risk in HC [group III, n = 5], P = NS), suggesting that DETA/NO failed to induce a delayed cardioprotective effect. These data demonstrate, for the first time, that HC blunts NO donor-induced late PC against myocardial infarction, implying that the inhibitory effects of HC on ischemia-induced and NO donor-induced late PC are caused by disruption of biochemical pathways distal to the generation of NO that triggers these adaptations.

• Authors: Xian-Liang Tang, Adam B Stein, Gregg Shirk, Roberto Bolli
• Journal: Basic research in cardiology (Basic Res Cardiol) Vol. 99 Issue 6 Pg. 395-403 (Nov 2004) ISSN: 0300-8428 [Print] Germany
• PMID: 15372283 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Nitric Oxide Donors
• Vasodilator Agents
• Nitric Oxide
• Cholesterol
• Bradykinin

Topics

• Animals
• Arteriosclerosis (pathology)
• Bradykinin (pharmacology)
• Cholesterol (blood)
• Consciousness (physiology)
• Heart Rate (drug effects)
• Hypercholesterolemia (metabolism, pathology)
• Ischemic Preconditioning, Myocardial
• Male
• Myocardial Infarction (metabolism, pathology, prevention & control)
• Nitric Oxide (metabolism)
• Nitric Oxide Donors (pharmacology)
• Rabbits
• Vasodilator Agents (pharmacology)