Cardiovascular responses to intravenous administration of insulin were studied in lightly anesthetized dogs treated with a neuromuscular blocking agent. An early transient pressor response was observed. This abrupt increase in arterial pressure appeared 2–9 min after insulin was given. It was accompanied by increases in cardiac output and right atrial pressure. It occurred in the presence of hyperglycemia and in the absence of hypoglycemia. It was not altered by glucagon but it could be antagonized by ganglionic and adrenergic blocking drugs and by pentobarbital. The response could be produced when insulin was given in the carotid artery in doses that caused no effect when injected in a systemic vein. The experiments suggest that insulin may have a direct action on the brain.

Forearm blood flow in normal human subjects was found to decrease progressively during intravenous infusions of norepinephrine as the rate of infusion increased (2). After 1 week of treatment with chlorothiazide, the same subjects responded to the same doses of norepinephrine with progressive increases in flow. 20, 1961 (1). Supported by Grant H-2644 from the National Heart Institute, Bethesda, Md., and aided by grants from the Iowa and American Heart Associations.t Established Investigator of the American Heart Association.§ Advanced Research Fellow of the American Heart Association.1 1 Postgraduate Trainee under Grant HTS-5367 from the National Heart Institute. that treated and untreated animals were available for study on the morning of the eighth day.The dogs were lightly anesthetized with 10 mg thiopental sodium per kg and treated with 0.3 mg decamethonium bromide per kg. A cuffed endotracheal tube was inserted immediately, and intermittent positive pressure breathing was instituted with a Harvard respiratory pump. Two cardiac catheters were introduced through the external jugular vein so that their tips lay in the main pulmonary artery and right atrium. Needles were inserted into the left carotid and femoral arteries and into a femoral vein. Pressures were recorded from the femoral artery and right atrium with Statham strain gauges. Drugs were given through the needle in the femoral vein. The catheter in the pulmonary artery was filled with indocyanine green dye and connected through a three-way stopcock to a dye reservoir and injection system. The needle in the carotid artery was connected through small-bore, nylon tubing to the cuvet of a Gilford densitometer. Dye curves were obtained by drawing blood through the densitometer with a constant speed pump after injections into the pulmonary artery. Endexpiratory CO2 concentration was monitored with a Spinco CO2 analyzer. Dye curves, CO2 concentration, and blood pressure were recorded with a Sanborn direct-writing oscillograph.Ventilation was adjusted by manipulating the controls on the respiratory pump so that end-expiratory CO2 concentration, after it became stable, was about 4 per cent. The rate and depth of breathing were not changed after this initial adjustment. Repeated doses of 0.075 mg decamethonium per kg were given at 20-minute intervals to maintain skeletal muscle relaxation. After the animal was prepared, 15 to 20 minutes were allowed for blood pressure and heart rate to become stable. Then l-norepinephrine bitartrate was infused intravenously at rates of 0.1, 0.2, and 0.4 Ag of norepinephrine base per kg per minute. Each dose was repeated once in each animal. The doses were given in random order both in the untreated and treated groups, using the same 6 X-6 Latin square (3). Observations on cardiac output, heart rate, and blood pressures were made immediately before and at the end of 2.5 minutes of norepinephrine infusion. Exactly 10 minutes were allowed between infusions. Electrically integrated mean right atrial pressures were recorded thro...

Intravenous administration of guanethidine to dogs causes an abrupt fall in systemic arterial pressure which is followed by a sustained increase. These studies were made to determine the nature of this biphasic response. Observations were made on dogs before and at frequent intervals after guanethidine was given. A fall in arterial pressure, an increase in cardiac output, and a decrease in peripheral resistance were observed within 10 sec; these changes lasted 40–50 sec. After the depressor phase, blood pressure and stroke volume increased while resistance returned to control levels. These acute changes subsided within 10–15 min. Ganglionic blockade augmented the pressor response and adrenergic blockade reduced it. Intra-arterial injection of guanethidine into perfused denervated forelegs caused brief vasodilatation followed by vasoconstriction. This response was qualitatively different from that seen with intra-arterial injection of norepinephrine. The results support indirectly the hypothesis that the systemic pressor response is caused by circulating catecholamines. The results demonstrate also that the drug has a local vasodilator action on the blood vessels of the foreleg.

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