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Free access | 10.1172/JCI109225
Department of Medicine, and the Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02118
Department of Pharmacology, and the Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02118
Cardiology Department, Boston City Hospital, Boston, Massachusetts 02118
Hypertension Department, Boston City Hospital, Boston, Massachusetts 02118
Thorndike Memorial Laboratory, Boston City Hospital, Boston, Massachusetts 02118
Find articles by Liang, C. in: JCI | PubMed | Google Scholar
Department of Medicine, and the Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02118
Department of Pharmacology, and the Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02118
Cardiology Department, Boston City Hospital, Boston, Massachusetts 02118
Hypertension Department, Boston City Hospital, Boston, Massachusetts 02118
Thorndike Memorial Laboratory, Boston City Hospital, Boston, Massachusetts 02118
Find articles by Gavras, H. in: JCI | PubMed | Google Scholar
Published November 1, 1978 - More info
The role of the renin-angiotensin system in mediating the circulatory and metabolic responses to hypoxia was studied in three groups of conscious dogs that were infused continuously with normal saline, teprotide (10 μg/kg per min), and saralasin (1 μg/kg per min), respectively. Hypoxia was produced by switching from breathing room air to 5 or 8% oxygen-nitrogen mixture. Plasma renin activity increased from 2.3±0.4 to 4.9±0.8 ng/ml per h during 8% oxygen breathing, and from 2.8±0.4 to 8.4±1.8 ng/ml per h during 5% oxygen breathing. As expected, cardiac output, heart rate, mean aortic blood pressure, and left ventricular dP/dt and dP/dt/P increased during both 5 and 8% oxygen breathing in the saline-treated dogs; greater increases occurred during the more severe hypoxia. Teprotide and saralasin infusion diminished the hemodynamic responses to 5% oxygen breathing, but did not affect the responses to 8% oxygen breathing significantly. In addition, the increased blood flows to the myocardium, kidneys, adrenals, brain, intercostal muscle, and diaphragm that usually occur during 5% oxygen breathing were reduced by both agents. These agents also reduced the increases in plasma norepinephrine concentration during 5% oxygen breathing, but had no effects on tissue aerobic or anaerobic metabolism.
In dogs pretreated with propranolol and phentolamine, administration of teprotide (0.5 mg/kg) during 5% oxygen breathing reduced mean aortic blood pressure and total peripheral vascular resistance, and increased cardiac output and heart rate, but did not affect left ventricular dP/dt, dP/dt/P, and end-diastolic pressure. Simultaneously, renal and myocardial blood flows increased and myocardial oxygen extraction decreased, while myocardial oxygen consumption did not change significantly.
These results suggest that the renin-angiotensin system plays an important role in the hemodynamic responses to severe hypoxia. It appears that angiotensin not only exerts a direct vasoconstrictor action, especially upon the coronary and renal circulations, but also potentiates the cardiovascular effects of sympathetic stimulation that occur during severe hypoxia.