Mechanism of the interaction of hypertension and hypercholesterolemia in atherogenesis: The effects of antihypertensive agents

Any alteration in the balance between serum lipids, platelets, hemodynamic factors, and the blood vessel wall may lead to the development of atherosclerosis. Hypertension and hypercholesterolemia are two major risk factors that accelerate the development of coronary heart disease. The mechanisms of the interactions of these two risk factors are examined in this paper. First, hypertension may be associated with focal or generalized endothelial injury or dysfunction. The altered endothelial functional integrity may predispose to platelet aggregation and altered vessel wall interaction, which may stimulate proliferation and growth of vascular cells. Second, elevated serum cholesterol levels may accelerate lipid deposition and formation of atherosclerotic plaques. In hypertension the rate of clearance of lipoprotein from the vessel wall may be reduced. Third, the sympathetic nervous system may be involved in both the development of hypertension and the alterations of lipid metabolism. Adrenergic activation, which increases blood pressure may also adversely affect lipid metabolism. This is in part α₁-adrenoceptor mediated. Selective α₁-inhibitors have been found to prevent or reduce atherosclerosis in experimental animals. Selective α₁-inhibitors may act at a number of sites on lipoprotein metabolic pathways to favorably influence serum lipids. Taken together, the relationship between hypertension and atherosclerosis involves complex mechanisms. A complete understanding of the mechanisms is of obvious importance.     

Dopamine: its potential for inducing ischemic left ventricular dysfunction

As an agent potentially capable of inducing ischemia in patients with coronary artery disease, dopamine administered intravenously was evaluated as a pharmacologic stress agent by supine radionuclide angiography, and the results were compared with ergometer exercise. In a preliminary group of 11 subjects (4 normal subjects and 7 patients with coronary disease), dopamine alone was administered in increments of 2.5 micrograms/kg per min to a maximum of 15 micrograms/kg per min. There were significant differences between exercise and dopamine in maximal stress heart rates, 129.3 +/- 30.0 versus 88.0 +/- 35.8 beats/min (p less than 0.05) in normal subjects and 118.9 +/- 21.1 versus 87.6 +/- 22.6 beats/min (p less than 0.05) in patients with coronary disease, as well as in maximal stress rate-pressure products, 213.3 +/- 51.4 versus 155.0 +/- 52.5 mm Hg/min X 10(2) (p less than 0.02) in normal subjects and 216.0 +/- 45.6 versus 161.0 +/- 48.6 mm Hg/min X 10(2) (p less than 0.003) in patients with coronary disease. As a result, in these patients the ejection fraction response was significantly different: -3.3 +/- 4.5% with exercise versus + 6.3 +/- 4.6% with dopamine (p less than 0.05). In a second group of 41 subjects (9 normal subjects and 32 patients with coronary disease), atropine (0.6 mg) was administered intravenously before and after every second dopamine dose increment. This produced statistically similar maximal stress heart rates as compared with exercise in all subjects, rate-pressure products in normal subjects and slightly higher values with dopamine in patients with coronary disease: 200.3 +/- 47.2 versus 183.1 +/- 43.0 (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)