Journal of cardiovascular pharmacology
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J. Cardiovasc. Pharmacol. · Jul 1982
Renal and cardiovascular responses to acute hypercapnic acidosis in conscious dogs: role of renin--angiotensin.
Patients with pulmonary dysfunction and CO2 retention have renal hemodynamic abnormalities accompanied by increased plasma renin activity. To determine if hypercapnia impairs renal function, particularly through the renin-angiotensin system, the effects of acute hypercapnic acidosis (HC), using 8.5% CO2, were measured in five unanesthetized dogs during (a) the intact state; (b) renin-angiotensin antagonism using either 1-sarcosine, 8-glycine angiotensin II ( [Sar1, Gly8] AII) or SQ 14,225; and (c) exogenous angiotensin II infusion. As partial arterial carbon dioxide pressure (PaCO2) increased (p less than 0.05) from control (C) of 35 +/- 1 (SEM) to 48 +/- 1 mm Hg during HC, arterial pH fell (p less than 0.05) from 7.36 +/- 0.01 to 7.24 +/- 0.005. ⋯ Although systemic vascular responses to exogenous AII infusion were similar, the renal vasoconstrictor response was antagonized during HC with unchanged GFR and renal blood flow. These findings indicate that despite activation of the renin-angiotensin system, acute hypercapnic acidosis is unassociated with impairment of renal function in unanesthetized dogs. This may be related to diminished renal vascular AII responsiveness during hypercapnia.
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J. Cardiovasc. Pharmacol. · Jul 1982
Lack of correlation of verapamil plasma level with cumulative protective effects against halothane--epinephrine ventricular arrhythmias.
The effect of verapamil, 0.2 mg/kg i.v. over 30 s, on the amount of epinephrine required to elicit a reproducible ventricular arrhythmia during 0.9% halothane in oxygen anesthesia was investigated in two groups of dogs after three consecutive doses of verapamil given at 90 (group I) and 120 min (group II) intervals, respectively. Verapamil caused a stepwise cumulative increase in the arrhythmogenic dose of epinephrine in both groups despite plasma verapamil levels that declined to low levels (28 and 22 ng/ml, respectively) between doses. ⋯ Changes in heart rate or blood pressure were similar among the three doses of verapamil in each group. These results can be interpreted to indicate that, unlike hemodynamic effects that appear to parallel plasma verapamil concentrations, the protective effects of verapamil against halothane--epinephrine ventricular arrhythmias may not be accurately reflected by plasma verapamil levels and may be significantly present when plasma levels are too low to cause measurable hemodynamic effects.