BAY k 8644, a calcium channel agonist, reverses hypotension in endotoxin-shocked rats.
The hypotension and depressed myocardial function frequently observed in endotoxin-induced shock are difficult to overcome pharmacologically. In this paper we demonstrate that the calcium channel agonist BAY k 8644 potently elevates blood pressure in endotoxin-shocked rats. A one time dose as low as 10 micrograms/kg of BAY k 8644 significantly elevated mean arterial pressure (MAP) in endotoxin-treated hypotensive rats while having minimal effects in normal rats. The maximum BAY k-induced percentage increase in MAP was greater in endotoxin-treated rats when compared with saline-treated control (153% vs. 120% increase respectively). BAY k 8644 also caused a dose-dependent decrease in heart rate of 37% in endotoxin-treated rats and 39% in control rats (NS vs. control). No differences in the regulatory properties of [3H]nitrendipine binding sites were discerned comparing control and endotoxin-treated rats. Thus, the enhanced activity of BAY k 8644 in hypotensive rats was not due to augmented affinity for the cardiac dihydropyridine binding site. These results demonstrate that the use of calcium channel agonists might represent a unique pharmacologic approach in pathologic states characterized by hypotension and diminished cardiac function.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004095:Dihydropyridines; D004305:Dose-Response Relationship, Drug; D008297:Male; D008861:Microsomes / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009568:Nitrendipine / Q000378:metabolism; D011725:Pyridines / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012772:Shock, Septic / Q000503:physiopathology*
D004095:Dihydropyridines; D011725:Pyridines; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C038806:1,4-dihydropyridine; D009568:Nitrendipine