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Hypertension and the coronary circulation. With special attention to endothelial regulation
D G Harrison1, C B Treasure, A Mügge
1Cardiology Division, Emory University School of Medicine, Atlanta, Georgia.
Insights
Calcium channel antagonists do not affect nitric oxide production in bovine aortic endothelial cells. This suggests these drugs do not impair endothelium-derived relaxing factor, important for vascular relaxation in hypertension.
Area of Science:
- Cardiovascular Pharmacology
- Endothelial Cell Biology
Background:
- Calcium channel antagonists are used for hypertension.
- Previous studies suggested they might impair endothelium-derived relaxing factor (EDRF).
- Direct effects on smooth muscle complicate interpretation.
Purpose of the Study:
- To investigate the effect of calcium channel antagonists on EDRF production in endothelial cells.
- To determine if these drugs alter nitric oxide release from bovine aortic endothelial cells (BAEC).
Main Methods:
- Used a chemiluminescence assay to measure nitric oxide release from BAEC.
- Incubated BAEC with diltiazem, verapamil, and nifedipine.
- Measured nitric oxide release under basal and bradykinin-stimulated conditions.
Main Results:
- Basal nitric oxide release was 0.2 nmol/100 mg protein.
- Bradykinin approximately doubled nitric oxide release.
- Diltiazem, verapamil, and nifedipine did not alter basal or bradykinin-stimulated nitric oxide release.
Conclusions:
- Calcium channel antagonists do not affect nitric oxide production by BAEC.
- EDRF production is not altered by these antagonists.
- Findings are consistent with the absence of L-type calcium channels in vascular endothelial cells.
Abstract:
Calcium channel antagonists are commonly used to treat chronic hypertension. Several studies of intact vascular tissues suggest that these agents may impair the production of the endothelium-derived relaxing factor and alter endothelium-dependent vascular relaxation. These studies are difficult to interpret because the calcium channel antagonist may have direct effects on vascular smooth muscle. In our study, a chemiluminescence assay was used to measure the release of nitrogen oxides from bovine aortic endothelial cells (BAEC) grown in monolayer. Under basal conditions, the release of nitrogen oxides was 0.2 nmol/100 mg protein and was increased approximately two-fold by 0.1 micrograms, bradykinin. Incubations with diltiazem, verapamil, and nifedipine for 60 min did not influence the basal and bradykinin-stimulated release of nitrogen oxides by BAEC. These data illustrate that the production of the endothelium-derived relaxing factor is not altered by the calcium channel antagonist, and are compatible with an absence of L-type calcium channels in vascular endothelial cells. Chronic hypertension produces myriad adverse effects in the coronary circulation. After coronary occlusion, infarct size, expressed as a function of myocardial mass perfused, is increased by 33%, and the wavefront of infarction from subendocardium to subepicardium is hastened. Both chronic and acute hypertension produce numerous abnormalities of coronary flow regulation. These include impairments of autoregulation, changes in vascular responsiveness, and alterations of endothelial cell function. Many of these may worsen the clinical consequences of ischemic heart disease, either by producing structural alterations of the coronary vasculature, or equally importantly, by altering coronary vascular responsiveness to either mechanical or neurohumoral stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)