PMID- 3576611
OWN - NLM
STAT- MEDLINE
DCOM- 19870602
LR  - 20190727
IS  - 0040-8727 (Print)
IS  - 0040-8727 (Linking)
VI  - 151
IP  - 1
DP  - 1987 Jan
TI  - The mechanism of centrally mediated cardiovascular actions of the three 
      structurally different calcium antagonists, verapamil, diltiazem and nicardipine, 
      in rats.
PG  - 65-80
AB  - Centrally mediated cardiovascular effects of the three structurally different 
      calcium antagonists (Ca-antagonists), i.e., verapamil, diltiazem and nicardipine, 
      were studied in rats. In conscious rats, when administered 
      intracerebroventricularly (i.c.v.) in doses of 0.3, 1 and 3 micrograms/kg/min for 
      30 min, all the three Ca-antagonists induced dose-dependent increases in mean 
      arterial pressure (MAP) and pulse rate (PR), whereas nicardipine administered 
      intravenously (i.v.) caused a decrease in MAP and an increase in PR. In 
      anesthetized rats all the three Ca-antagonists in a dose of 3 micrograms/kg/min 
      for 60 min i.c.v. significantly potentiated the hypotensive and bradycardic 
      effects of i.c.v. clonidine. Nicardipine, in a dose of 0.3 microgram/kg/min for 
      60 min i.c.v., attenuated the hypotensive and bradycardic effects of i.c.v. 
      clonidine or B-HT 920, an alpha 2-adrenoceptor agonist, in anesthetized rats, 
      whereas it did not modify the cardiovascular effect of i.c.v. angiotensin II or 
      gamma-aminobutylic acid in conscious rats. Nicardipine, in a dose of 0.3 
      microgram/kg/min for 60 min i.v., did not modulate the hypotensive and 
      bradycardic effects of i.c.v. clonidine. 3-Isobutyl-l-methylxanthine (IBMX), a 
      cyclic AMP phosphodiesterase inhibitor, in a dose of 3 micrograms/kg/min for 60 
      min i.c.v., also attenuated the hypotensive and bradycardic effects of i.c.v. 
      clonidine. Potentiation by the three i.c.v. Ca-antagonists of the hypotensive and 
      bradycardic effects of clonidine would be explainable if their inhibitory effect 
      on Ca-influx is exerted at presynaptic nerve terminals but not at postsynaptic. 
      The mechanisms of the cardiovascular effect of i.c.v. Ca-antagonists still remain 
      to be elucidated but may be independent of a central alpha 2-adrenoceptor 
      mechanism. Dihydropyridine Ca-antagonists like nicardipine are also potent 
      inhibitor of cyclic AMP phosphodiesterase. Since IBMX mimicked the effect of 
      nicardipine, the effect of a low dose of i.c.v. nicardipine in attenuating the 
      hypotensive and bradycardic effects of i.c.v. clonidine may be mediated by 
      inhibition of cyclic AMP phosphodiesterase in the central nervous system.
FAU - Imai, Y
AU  - Imai Y
FAU - Abe, K
AU  - Abe K
FAU - Sasaki, S
AU  - Sasaki S
FAU - Minami, N
AU  - Minami N
FAU - Seino, M
AU  - Seino M
FAU - Yoshinaga, K
AU  - Yoshinaga K
FAU - Taira, N
AU  - Taira N
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Japan
TA  - Tohoku J Exp Med
JT  - The Tohoku journal of experimental medicine
JID - 0417355
RN  - CJ0O37KU29 (Verapamil)
RN  - CZ5312222S (Nicardipine)
RN  - EE92BBP03H (Diltiazem)
SB  - IM
MH  - Animals
MH  - Blood Pressure/drug effects
MH  - Brain/*drug effects
MH  - Cardiovascular System/*drug effects
MH  - Diltiazem/*pharmacology
MH  - Heart Rate/drug effects
MH  - Injections, Intravenous
MH  - Injections, Intraventricular
MH  - Male
MH  - Nicardipine/*pharmacology
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Verapamil/*pharmacology
EDAT- 1987/01/01 00:00
MHDA- 1987/01/01 00:01
CRDT- 1987/01/01 00:00
PHST- 1987/01/01 00:00 [pubmed]
PHST- 1987/01/01 00:01 [medline]
PHST- 1987/01/01 00:00 [entrez]
AID - 10.1620/tjem.151.65 [doi]
PST - ppublish
SO  - Tohoku J Exp Med. 1987 Jan;151(1):65-80. doi: 10.1620/tjem.151.65.