Effects of indomethacin on hormonal and blood pressure responses to captopril in spontaneously hypertensive rats.
The possible role of vasodilatory prostanoids in the antihypertensive action of captopril was investigated in spontaneously hypertensive rats (SHR). Captopril (100 mg/kg/day for 5 days) decreased systolic blood pressure and increased water consumption, urine excretion and plasma renin activity (PRA). It also enhanced the urinary excretion of the prostacyclin metabolite 6-keto-PGF1 alpha, but did not change the excretion of PGE2. Indomethacin (3 mg/kg/day), given both alone and in combination with captopril, reduced markedly the urinary excretions of 6-keto-PGF1 alpha and PGE2 but did not alter PRA, compared with corresponding groups without indomethacin. The suppression of prostanoid synthesis caused by indomethacin did not affect the antihypertensive effect of captopril or the basal blood pressure in SHR. Neither did indomethacin influence drinking or urine excretion in SHR not receiving captopril, but it reduced the dipsogenic and diuretic effects of captopril. The results suggest that captopril augments the production of vasodilatory prostacyclin. Yet prostanoids have no significant role in the antihypertensive mechanism of captopril in SHR.
Säynävälammi
P
P
Department of Biomedical Sciences, University of Tampere, Findland.
Arvola
P
P
Kuismanen
K
K
Seppälä
E
E
Nurmi
A K
AK
Manninen
V
V
Vapaatalo
H
H
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology*; D004326:Drinking / Q000187:drug effects; D011464:Epoprostenol / Q000097:blood; D006973:Hypertension / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D012083:Renin / Q000097:blood
D015121:6-Ketoprostaglandin F1 alpha; D002216:Captopril; D011464:Epoprostenol; D012083:Renin; D007213:Indomethacin