PMID- 6100756
OWN - NLM
STAT- MEDLINE
DCOM- 19860625
LR  - 20131121
IS  - 0952-1178 (Print)
IS  - 0952-1178 (Linking)
VI  - 2
IP  - 3
DP  - 1984 Dec
TI  - Effect of central administration of MK-422 (the diacid form of enalapril) on the 
      development of hypertension in the spontaneously hypertensive rat.
PG  - S63-6
AB  - Intracerebroventricular (i.c.v.) administration of captopril attenuates the 
      development of hypertension in spontaneously hypertensive rats (SHR). To 
      determine whether these effects are related to inhibition of 
      angiotensin-converting enzyme we assessed the effects of chronic i.c.v. 
      administration of MK-422 (a converting enzyme inhibitor chemically unrelated to 
      captopril) on arterial pressure and vascular reactivity in young (seven-week-old) 
      male SHR. MK-422 (0.2 or 1.0 microgram/h, osmotic mini pump) was infused into the 
      lateral ventrical for 4 weeks. Control SHR received artificial CSF i.c.v., or 0.2 
      microgram/h MK-422 i.v. Vascular reactivity to phenylephrine, vasopressin and 
      direct sympathetic nerve stimulation was assessed in renal and mesenteric 
      vascular beds using miniaturized pulsed Doppler flow probes. MK-422 attenuated 
      the development of hypertension. Arterial pressure at 4 weeks of treatment was: 
      SHR-i.c.v. MK-422 (0.1 microgram/h): 137 +/- 3.4; (1.0 microgram/h): 138 +/- 2.9; 
      SHR i.v. MK-422 176 +/- 4.5 and SHR control: 168 +/- 4.9 mmHg (P less than 0.01). 
      SHR-i.c.v. MK-422 showed significantly attenuated increases in mesenteric 
      vascular reactivity in response to vasoconstrictors, nerves and sympathetic 
      nervous stimulation. Dose and frequency response curves were characterized by a 
      shift to the right and a significant decrease in the slopes. In conclusion, both 
      captopril and MK-422 prevent the development of hypertension in SHR, presumably 
      by blocking angiotensin-converting enzyme, suggesting that the brain 
      renin-angiotensin system contributes to the pathogenesis of hypertension in that 
      model.
FAU - Berecek, K H
AU  - Berecek KH
FAU - Nagahama, S
AU  - Nagahama S
FAU - Oparil, S
AU  - Oparil S
LA  - eng
GR  - HL-22544/HL/NHLBI NIH HHS/United States
GR  - HL-25451/HL/NHLBI NIH HHS/United States
GR  - HL-31515/HL/NHLBI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - J Hypertens Suppl
JT  - Journal of hypertension. Supplement : official journal of the International 
      Society of Hypertension
JID - 8501422
RN  - 0 (Antihypertensive Agents)
RN  - 69PN84IO1A (Enalapril)
RN  - 9G64RSX1XD (Captopril)
RN  - GV0O7ES0R3 (Enalaprilat)
SB  - IM
MH  - Animals
MH  - Antihypertensive Agents/*therapeutic use
MH  - Blood Pressure/drug effects
MH  - Captopril/therapeutic use
MH  - Dose-Response Relationship, Drug
MH  - Drug Evaluation, Preclinical
MH  - Electric Stimulation
MH  - Enalapril/*analogs & derivatives/therapeutic use
MH  - Enalaprilat
MH  - Hypertension/physiopathology/*prevention & control
MH  - Male
MH  - Rats
MH  - Rats, Inbred SHR/*physiology
MH  - Rats, Inbred Strains/*physiology
MH  - Sympathetic Nervous System/drug effects/physiology
MH  - Time Factors
MH  - Vascular Resistance/drug effects
EDAT- 1984/12/01 00:00
MHDA- 1984/12/01 00:01
CRDT- 1984/12/01 00:00
PHST- 1984/12/01 00:00 [pubmed]
PHST- 1984/12/01 00:01 [medline]
PHST- 1984/12/01 00:00 [entrez]
PST - ppublish
SO  - J Hypertens Suppl. 1984 Dec;2(3):S63-6.