title: Effects of prolonged phenylephrine infusion on cardiac adrenoceptors and calcium channels.
abstract: Effects of prolonged in vivo infusion of phenylephrine upon receptor binding and cardiac contractility were studied in Sprague-Dawley rats. A 1-hr i.v. infusion of phenylephrine (3 mg/kg/hr) resulted in a sustained 50% increase in diastolic blood pressure and 5% increase in heart rate. Chronic (6-day) infusion (3 mg/kg/hr) utilizing Alzet mini-osmotic pumps maintained plasma concentrations of phenylephrine at 1.0 microgram/ml, depleted myocardial norepinephrine stores 8-fold and resulted in a modest cardiac hypertrophy. Density and affinity of myocardial adrenoceptors and calcium channels were quantified by analyzing saturation isotherms of radioligand binding. [3H]Prazosin, [3H]dihydroalprenolol and [3H]nitrendipine bound specifically and with high affinity to cardiac alpha-1 and beta adrenoceptors and calcium channels, respectively. As measured by Scatchard analyses, phenylephrine infusion significantly decreased the maximum number (Bmax) of specific [3H]prazosin binding sites by 39% (430 +/- 20 vs. 263 +/- 16 fmol/mg of protein; P less than .05). Chronic phenylephrine treatment also decreased the Bmax for [3H]dihydroalprenolol binding by 31% (124 +/- 3.3 vs. 86 +/- 6.6 fmol/mg of protein; P less than .05) and the Bmax for [3H]nitrendipine binding by 32% (342 +/- 8.8 vs. 235 +/- 6.7 fmol/mg of protein; P less than .05). Binding affinities (Kd) of [3H]prazosin, [3H]dihydroalprenolol and [3H]nitrendipine remained unchanged. Administration of vehicle alone or surgical manipulation due to osmotic pump implantation did not affect either the density or affinity of [3H]prazosin, [3H]dihydroalprenolol or [3H]nitrendipine binding. Contractile responses to phenylephrine were studied in isolated ventricular strips to determine the functional significance of alpha-1 adrenoceptor down-regulation.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D004082:Dihydroalprenolol / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D007473:Ion Channels / Q000187:drug effects*; D007700:Kinetics; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D009568:Nitrendipine / Q000378:metabolism; D010656:Phenylephrine / Q000008:administration & dosage / Q000494:pharmacology*; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects*
chemical_list: D007473:Ion Channels; D011941:Receptors, Adrenergic; D010656:Phenylephrine; D004082:Dihydroalprenolol; D009568:Nitrendipine; D002118:Calcium; D011224:Prazosin