Absence of hypertension despite chronic marked elevations in plasma norepinephrine in conscious dogs.
To better define the mechanisms of blood pressure control in states of catecholamine excess, we infused norepinephrine for 28 days using subcutaneously implanted osmotic pumps in dogs previously instrumented for monitoring left ventricular dynamics and cardiac output. Plasma norepinephrine rose from 238 +/- 27 to 4346 +/- 952 pg/ml at 21 days, while epinephrine and dopamine levels did not change. Heart rate fell from 85 +/- 4 to 63 +/- 6 beats/min, while arterial pressure was unchanged from baseline. Total peripheral resistance rose 0.011 +/- 0.003 mm Hg/ml/min from a control value of 0.029 +/- 0.002 mm Hg/ml/min, and cardiac output decreased 1093 +/- 292 ml/min from a baseline level of 3575 +/- 156 ml/min. Since stroke volume did not change, the maintenance of arterial pressure is related to decreases in cardiac output secondary to bradycardia. Buffering mechanisms are responsible for maintenance of systemic arterial pressure because hexamethonium and atropine caused hypertension. Although left ventricular end-diastolic pressure, end-diastolic diameter, shortening, rate of change of pressure, velocity of myocardial shortening, cardiac work, stroke work, and the double product did not change significantly during the study, postmortem examination demonstrated biventricular hypertrophy. Thus, despite markedly elevated catecholamine levels and no elevation of systemic arterial pressure, myocardial hypertrophy developed. These studies lend support to the hypothesis that norepinephrine may be a direct myocardial tropic hormone and suggest that intense activation of reflex buffering mechanisms maintains blood pressure in the normal range during chronic catecholamine infusion.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002302:Cardiac Output / Q000187:drug effects*; D006332:Cardiomegaly / Q000209:etiology; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000097:blood / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects*
D001285:Atropine; D009638:Norepinephrine