Long-term hypotensive effect of beta-agonist in conscious dogs.

The purpose of this study was to investigate the arterial pressure response to long-term administration of beta-agonists in the chronically instrumented conscious animal model. Chronically instrumented dogs were given intravenous infusions of ritodrine (2 micrograms.kg-1.min-1) for a period of 2 wk. Several cardiovascular and renal parameters were monitored before, during, and after the ritodrine infusion, and renal function curves were constructed. After the 1st wk of infusion, a new steady state was reestablished, and this was characterized by hypotension, reduced plasma protein concentration, elevated cardiac output, expanded extracellular fluid space, and near normal levels of activity of renin-angiotensin-aldosterone systems. The renal function curve during ritodrine infusion shifted to the left with no change in slope. We propose the following: 1) the persistence of hypotension is most probably related to the resetting of the arterial pressure-kidney blood volume servocontrol mechanisms, and 2) the persistent elevation of cardiac output and reduction in peripheral resistance are most probably related to increased oxygen and nutrient demand during beta-agonist infusions.

Analysis of the cardiovascular effects of arginine vasopressin in conscious dogs.

The effects of physiological elevations in arginine vasopressin on the cardiovascular system were studied in a group of nine conscious, chronically instrumented dogs. The animals were studied under normal conditions (plasma vasopressin, 4.1 +/- 0.4 pg/ml), after 24 hours of dehydration (plasma vasopressin, 7.3 +/- 1.5 pg/ml), after a 30-minute vasopressin infusion at 2.6 ng/kg/min (plasma vasopressin, 96.6 +/- 8.1 pg/ml). These increases in vasopressin concentration resulted in no change in arterial pressure and significant changes in the following: a 13 and 29% decrease in resting cardiac output during dehydration and acute infusion, respectively; a 26% reduction in heart rate during acute infusion; a 12 and 54% increase in total peripheral resistance during dehydration and acute infusion; a 16 and 22% reduction in mean circulatory filling pressure during dehydration and chronic vasopressin infusion. In addition, maximum pumping ability of the heart was reduced 16 and 31% during dehydration and acute infusion, respectively. These data suggest that elevations of vasopressin such as those occurring during dehydration or volume depletion potentially may affect cardiovascular performance by three mechanisms: greatly increasing resistance to flow, reducing heart rate, suppressing the pumping ability of the heart.

Effects of sodium intake on steady-state potassium excretion.

The effects of changes in sodium intake on the steady-state relationship between plasma potassium concentration and potassium excretion were studied in 15 chronically adrenalectomized dogs. Throughout the experiments the dogs received aldosterone at a rate of 50 micrograms/day and methylprednisolone at 1 mg/day. The relationship between plasma potassium and steady-state potassium excretion was obtained by changing potassium intake from 10 to 30 to 100 meq/day, each level being maintained for 7-10 days. At the conclusion of each period at a given level of potassium intake, plasma potassium and excretion were measured and plotted, plasma potassium being the independent variable. Such a relationship was obtained while the dogs were on three different levels of sodium intake: 10, 100, and 200 meq/day. The curves from the data obtained at 100 and 200 meq/day sodium intake both were shifted to the left of the curve obtained at 10 meq/day (P less than 0.05), although the 100 and 200 meq/day curves were not different from each other. On the basis of these data one could predict that, at a plasma potassium concentration of 4.0 meq/liter, the animals would excrete potassium at a rate of 17 meq/day on a 10 meq/day sodium intake, 37 meq/day on a 100 meq/day sodium intake, and 47 meq/day on a 200 meq/day sodium intake. Urine flow and electrolyte concentration data are consistent with the hypothesis that the sodium intake effect on potassium excretion was mediated through increases in distal nephron flow rate and decreases in distal nephron potassium concentration.