Role of angiotensin II in reflex tachycardia during hypotension caused by a calcium channel blocker.
Blood pressure and heart rate were measured by telemetry in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) to investigate the contribution of angiotensin II to the reflex tachycardia resulting from exaggerated hypotension caused by a high dose of a calcium channel blocker. Pre-treatment with TCV-116, an angiotensin II AT1 receptor antagonist, or enalapril partially attenuated the reflex tachycardia induced by manidipine, but TCV-116 had almost no effect on the sinus tachycardia induced by isoproterenol. The suppressive effects of TCV-116 against the reflex tachycardia tended to be more obvious in WKY than in SHR, though the difference was not statistically significant. Concurrent administration of propranolol almost completely inhibited both the reflex tachycardia and the sinus tachycardia in SHR and WKY, indicating that the sympathetic nervous system contributes to both types of tachycardia. We demonstrated that angiotensin II may be involved in the reflex tachycardia induced by calcium channel blockers probably via activation of some component of the sympathetic nervous system other than postsynaptic factors at the sinus node.
Sato
K
K
Drug Safety Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
Chatani
F
F
Sato
S
S
D000804:Angiotensin II / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D004656:Enalapril / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D007022:Hypotension / Q000139:chemically induced / Q000150:complications*; D009578:Nitrobenzenes; D010879:Piperazines; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012018:Reflex; D013610:Tachycardia / Q000209:etiology* / Q000503:physiopathology*; D013616:Tachycardia, Sinus / Q000503:physiopathology; D013686:Telemetry; D013777:Tetrazoles; D013997:Time Factors
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009578:Nitrobenzenes; D010879:Piperazines; D013777:Tetrazoles; D000804:Angiotensin II; D004656:Enalapril; C054218:manidipine; D011433:Propranolol; C077793:candesartan cilexetil