Mechanisms responsible for sustained hypotension after captopril treatment.
OBJECTIVE
To investigate new aspects of the relationship between sustained reduction of blood pressure and alteration of cardiovascular structure and function after cessation of early captopril treatment.


METHODS
Spontaneously hypertensive rats (SHR) were given captopril 20 mg/kg per day (n = 13) or 100 mg/kg per day (n = 12) from the intra-uterine period to age 16 weeks and then the treatment was stopped. Age-matched untreated SHR (n = 16) and Wistar-Kyoto (WKY) rats (n = 17) served as controls. The experiments were carried out at 40 weeks.


RESULTS
Withdrawal of captopril treatment resulted in a rapid rebound of SBP to a level close to that of untreated SHR in the low-dose group, whereas a persistently lower SBP was maintained in the high-dose group. Both doses of captopril treatment completely prevented wall hypertrophy either of arteriolar resistance vessels or of muscular vessels. Captopril decreased left ventricular mass:body weight ratio dose-dependently. High-dose captopril improved the resting and stress systolic and diastolic function. Thoracic angiotensin converting enzyme levels were dose-dependently reduced by captopril treatment. The curves of perfusion pressure response to incremental doses of phenylephrine shifted to the right in both captopril treatment groups compared with those of the control SHR. Addition of L-NAME and L-arginine to the perfusate augmented or attenuated the vasoconstrictor activity in all of the rats, whereas high-dose captopril totally restored the abnormal hypersensitivity to L-NAME and caused less attenuation in response to L-arginine in the control SHR.


CONCLUSIONS
The persistent lower blood pressure caused by early captopril treatment was ascribed mainly to its sustained normalization of structure and function of resistance vessels, which may be partly mediated by the improvement of endothelial cell function. The persistent reduction of angiotensin converting enzyme activity in blood vessel wall attenuated left ventricular hypertrophy, and the improvement of cardiac systolic and diastolic function may also contribute to the sustained hypotensive effect.
Chen
D G
DG
Hypertension Division, First Affiliated Hospital, Fujian Medical College, Fuzhou, People's Republic of China.
Jin
X Q
XQ
Wang
H J
HJ
Chen
S C
SC
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001158:Arteries / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002216:Captopril / Q000627:therapeutic use*; D005260:Female; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014655:Vascular Resistance / Q000187:drug effects
D000959:Antihypertensive Agents; D002216:Captopril; D007703:Peptidyl-Dipeptidase A