title: Azelnidipine attenuates cardiovascular and sympathetic responses to air-jet stress in genetically hypertensive rats.
abstract: Azelnidipine is a new dihydropyridine calcium channel blocker that causes minimal stimulation of the sympathetic nervous system despite its significant depressor effect. In the present study, we examined the effects of oral or intravenous administration of azelnidipine on cardiovascular and renal sympathetic nerve activity (RSNA) responses to air-jet stress in conscious, unrestrained stroke-prone spontaneously hypertensive rats. Oral administration of high-dose azelnidipine (10 mg/kg per day) or nicardipine (150 mg/kg per day) for 10 days caused a significant and comparable decrease in blood pressure, but low-dose azelnidipine (3 mg/kg per day) did not. Air-jet stress increased mean arterial pressure (MAP), heart rate (HR) and RSNA. High-dose azelnidipine significantly attenuated the increases in MAP, HR and RSNA in response to air-jet stress while nicardipine did not. Low-dose azelnidipine significantly attenuated the pressor response with a trend of decrease in RSNA. Intravenous injection of azelnidipine induced a slowly developing depressor effect. To obtain a similar time course of decrease in MAP by azelnidipine, nicardipine was continuously infused at adjusted doses. Both drugs increased HR and RSNA significantly, while the change in RSNA was smaller in the azelnidipine group. In addition, intravenous administration of azelnidipine attenuated the responses of MAP, HR, and RSNA to air-jet stress; by comparison, the inhibitory actions of nicardipine were weak. In conclusion, oral or intravenous administration of azelnidipine inhibited cardiovascular and sympathetic responses to air-jet stress. This action of azelnidipine may be mediated at least in part by the inhibition of the sympathetic nervous system.
authors.affiliation: Department of Cardiovascular Medicine, Nephrology and Neurology, School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Minori
authors.initials: M
authors.lastname: Nakamoto
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ohya
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sakima
authors.forename: Masanobu
authors.initials: M
authors.lastname: Yamazato
authors.forename: Shuichi
authors.initials: S
authors.lastname: Takishita
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001383:Azetidinecarboxylic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D002319:Cardiovascular System / Q000187:drug effects* / Q000503:physiopathology; D004095:Dihydropyridines / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006706:Homeostasis / Q000502:physiology; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D007275:Injections, Intravenous; D008297:Male; D009529:Nicardipine / Q000008:administration & dosage / Q000627:therapeutic use; D051381:Rats; D011918:Rats, Inbred SHR; D013312:Stress, Physiological / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D013997:Time Factors
chemical_list: D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D001383:Azetidinecarboxylic Acid; D009529:Nicardipine; C061679:azelnidipine