PMID- 1706799 OWN - NLM STAT- MEDLINE DCOM- 19910426 LR - 20190724 IS - 0160-2446 (Print) IS - 0160-2446 (Linking) VI - 16 IP - 4 DP - 1990 Oct TI - Modulation of adrenoceptor-mediated cardiovascular effects by short-term in vivo infusion of isoproterenol in rats. PG - 584-93 AB - After a 16-h in vivo infusion period of isoproterenol (400 micrograms/kg/h) from a minipump implanted subcutaneously (s.c.) in rats, we observed an increase in heart weight due to tissue edema. In isolated perfused heart preparations, the EC50s of isoproterenol to induce positive inotropy and increase in coronary flow were increased approximately 7 and 4 times, respectively. Isoproterenol dose-response curves performed in trachea preparations, were shifted to the right by about fivefold as compared with the control group. In the presence of phentolamine, the isoproterenol induced maximal relaxation in the isolated aorta from isoproterenol-pretreated animals was reduced from 46.5 to 9.2% as compared with saline-pretreated rats. In the absence of phentolamine, the epinephrine (EPI) and norepinephrine (NE) cumulative dose-response curves in this preparation were not affected by isoproterenol pretreatment with respect to EC50 and maximal effect. However, in the presence of phentolamine, the contractile response to a supramaximal dose of NE (10 microM) amounted to 30 and 70% in the saline- and isoproterenol-pretreated rats, respectively. In the presence of both phentolamine and propranolol, a similar response of 70% was observed by this supramaximal dose of agonist in the saline-pretreated rats as well. In anesthetized rats, 120 min after removal of the minipumps, sodium nitroprusside induced increase in heart rate (HR) was reduced after isoproterenol pretreatment, whereas for salbutamol the decrease in diastolic blood pressure (DBP) was also reduced. As compared with salbutamol, a marked increase was observed in the ratio of mean arterial blood pressure (MAP) to HR for SNP after isoproterenol pretreatment. The phenylephrine-induced increase in MAP was increased after isoproterenol pretreatment. We conclude that in the pathogenesis of heart failure the beta-adrenoceptor-mediated effects of catecholamines are attenuated and alpha-adrenoceptor-mediated effects become progressively important. FAU - Vleeming, W AU - Vleeming W AD - Department of Pharmacotherapy, Faculty of Pharmacy, University Utrecht, The Netherlands. FAU - van Rooij, H H AU - van Rooij HH FAU - Wemer, J AU - Wemer J FAU - Porsius, A J AU - Porsius AJ LA - eng PT - Journal Article PL - United States TA - J Cardiovasc Pharmacol JT - Journal of cardiovascular pharmacology JID - 7902492 RN - 0 (Receptors, Adrenergic, beta) RN - L628TT009W (Isoproterenol) SB - IM MH - Animals MH - Aorta, Thoracic MH - Cardiovascular System/*drug effects MH - Coronary Circulation/drug effects MH - Dose-Response Relationship, Drug MH - Hemodynamics/drug effects MH - In Vitro Techniques MH - Infusion Pumps MH - Isoproterenol/administration & dosage/*pharmacology MH - Male MH - Myocardial Contraction/drug effects MH - Rats MH - Rats, Inbred Strains MH - Receptors, Adrenergic, beta/*drug effects MH - Stimulation, Chemical MH - Time Factors MH - Trachea EDAT- 1990/10/01 00:00 MHDA- 1990/10/01 00:01 CRDT- 1990/10/01 00:00 PHST- 1990/10/01 00:00 [pubmed] PHST- 1990/10/01 00:01 [medline] PHST- 1990/10/01 00:00 [entrez] AID - 10.1097/00005344-199010000-00009 [doi] PST - ppublish SO - J Cardiovasc Pharmacol. 1990 Oct;16(4):584-93. doi: 10.1097/00005344-199010000-00009.