Jerry B. Scott

The Mechanism of the Vasodilator Action of Potassium

Summary In the dog gracilis muscle and forelimb, ouabain blocked or reversed hypokalemic constriction and suppressed, blocked or reversed hyperkalemic vasodilation. This suggests that the vasodilator action of potassium is related to stimulation of membrane Na+ -K+ ATPase activity resulting in hyper-polarization and relaxation of the vascular smooth muscle cell. Exercise dilation was only slightly modified in a muscle in which potassium vasodilation was greatly suppressed, suggesting a minor role for potassium in sustained exercise hyperemia.

Effect of epinephrine, norepinephrine and serotonin upon systemic small and large vessel resistance.

Locally injected epinephrine and norepinephrine elevate dog foreleg total vascular resistance primarily through small vessel constriction. Serotonin does not significantly change total resistance, constricts large arteries and veins and dilates small vessels.

Effects of Indomethacin on Local Blood Flow Regulation in Canine Heart and Kidney

Summary In two series of experiments we studied the effects of indomethacin on (a) coronary reactive hyperemia and, (b) renal blood flow, autoregulation, and reactive dilation. Coronary blood flow was measured in closed-chest dogs. Reactive hyperemia was induced by coronary occlusion for 5 and 15 sec. Indomethacin, an inhibitor of prostaglandin synthesis, was infused intra-arterially in doses of 90-200 mg over periods ranging from 30-120 min. Coronary reactive hyperemia was not affected by indomethacin. The canine renal vascular bed was studied under conditions of natural flow, controlled flow, and controlled pressure. Intra-arterial infusion of 90 mg of indomethacin over a 30- to 60-min period caused increased renal vascular resistance and an attenuation of reactive dilation (induced by stopping renal blood flow for 90 sec). Indomethacin slightly attenuated the autoregulatory response to decreasing perfusion pressures, but did not affect the response to increasing pressures. Thus the study fails to provide evidence for participation of the prostaglandins in regulation of coronary blood flow and suggests only minimal participation of prostaglandings in renal blood flow regulation. The authors wish to thank Mr. B. T. Swindall and Mr. G. W. Gamble for valuable surgical assistance, and Mrs. J. Johnston and Mrs. M. Mason for technical assistance.

Effect of Hypokalemia and Hypomagnesemia Produced by Hemodialysis on Vascular Resistance in Canine Skeletal Muscle ROLE OF POTASSIUM IN ACTIVE HYPEREMIA

Hemodialysis was used to study the effect of an acute local decrease in plasma [K+] or [Mg2+] or in both on vascular resistance in skeletal muscle. A dialyzer was placed in the arterial supply of the collateral-free gracilis muscle of the dog and blood flow was held constant while measuring perfusion pressure. Pressure increased linearly with decreased [K+] down to 0.2 mEq/liter. A 50% decrease in [K+] produced a 12% increase in resistance. Prolonged hypokalemia produced a sustained increase in perfusion pressure and a decreased responsiveness to close arterial injection of norepinephrine. Removal of up to 84% of the plasma Mg2+ produced no effect, either alone or in conjunction with hypokalemia. When the potassium level of the perfusing blood was changed from normal to hypokalemic during the dilation brought on by simulated exercise, the resistance did not change. In addition, the magnitude of the resistance changes seen during exercise were much greater than could be induced by local changes in plasma [K+] alone. It is concluded that hypokalemia produces active constriction of vascular smooth muscle. However, this study fails to lend support to the idea that potassium alone is responsible for exercise dilation.

Flow through collapsible tubes at high Reynolds numbers.

The pressure-flow relationships of collapsible tubes were studied utilizing the Starling resistor model. Reynolds numbers much higher than previously reported were used to simulate high cardiac output states. Alterations which occur in vivo, including longitudinal tension, stretch, tubing diameter, length, and outflow resistance were also simulated and systematically investigated. The pressure-flow curves showed an initial rising phase, a plateau phase, as well as a late-rising phase which has not been reported previously. Self-induced oscillations occurred during the plateau phase and persisted throughout the late-rising phase. These perturbations were markedly increased by longitudinal tension and stretch, but were attenuated by increased diameter, length, and outflow pressure. These instabilities may prove to be an explanation for the “venoiia hum.

Mechanism of the acute pressor action of hypokalemia, hypomagnesemia, and hypo-osmolality

Abstract The hemodynamic mechanism of the acute pressor action of hypokalemia, hypomagnesemia, and hypo-osmolality was studied in the anesthetized dog. The electrolyte changes were first produced rapidly (within 5 minutes) by a dilutional technique and then more slowly (within 50 minutes) utilizing a potent diuretic and modified Ringers solution. Blood pressure and cardiac output were measured and total peripheral resistance was calculated. The data suggest that the blood pressure rises because of effects on the periphery when the electrolyte changes are produced rapidly by the dilutional technique and because of effects on both the heart and periphery when the electrolyte changes are produced more slowly by the diuretic technique.

Effect of pH Change upon Systemic Large and Small Vessel Resistance

In the dog foreleg acute increase and decrease of hydrogen ion concentration is associated with active small vessel dilatation and constriction, respectively, through some direct effect upon vascular smooth muscle. These small vessel resistance changes do not affect total resistance in the intact leg because of directionally opposite active changes in artery resistance. The latter response appears to be related to central nervous connections and perhaps to circulating or locally released epinephrine, norepinephrine or unknown vasoactive substances.

Flow through collapsible tubes at low Reynolds numbers. Applicability of the waterfall model.

The applicability of the waterfall model was tested using the Starling resistor and different viscosities of fluids to vary the Reynolds number. The waterfall model proved adequate to describe flow in the Starling resistor model only at very low Reynolds numbers (Reynolds number <1). Blood flow characterized by such low Reynolds numbers occurs only in the microvasculature. Thus, it is inappropriate to apply the waterfall model indiscriminately to flow through large collapsible veins. Circ Res 47: 68-73, 1980

Role of the myogenic response in exercise hyperemia.

Abstract The hemodynamic effects of passive decreases in vascular transmural pressure produced by increases in extravascular pressure were compared with the hemodynamic responses to nerve stimulation in the blood perfused in vitro canine gracilis muscle. These studies were performed in an attempt to isolate the proposed contribution of the myogenic response to active hyperemia in skeletal muscle. In order to separate vascular transmural pressure changes from other mechanisms associated with an active muscle, a special muscle perfusion chamber was designed. This chamber allowed pulsatile changes in extravascular pressure to be made in a passive muscle, with similar magnitude and frequency as would occur in an active muscle. Pulsatile changes in extravascular pressure over the range 10 to 50 mm Hg at rates of 2 and 5 pulses per second failed to elicit an active vascular response. Thus these studies fail to support a role for the myogenic response in twitch exercise of canine skeletal muscle.

Reduction of Exercise Dilation by Theophylline

Summary The canine gracilis muscle was exercised at constant flow before and during administration of theophylline at a rate which completely blocked the vasodilator response produced by injected adenosine. Exercise dilation was significantly attenuated during infusion of theophylline. This suggests a role for adenosine in the exercise dilation seen in the canine gracilis muscle during constant flow perfusion. The authors acknowledge the able technical assistance of George Gamble and William Stoffs.