TY - JOUR
T1 - No evidence on significant roles of the prostaglandin-thromboxane and kallikrein-kinin system in the antihypertensive effect of MK 421 in rats made hypertensive by norepinephrine or vasopressin
AU - Yasujima, M.
AU - Abe, K.
AU - Tanno, M.
AU - Kohzukl, M.
AU - Kasai, Y.
AU - Kanazawa, M.
AU - Omata, K.
AU - Sato, M.
AU - Takeuchi, K.
AU - Yoshinaga, K.
PY - 1987
Y1 - 1987
N2 - Inhibition of angiotensin converting enzyme by MK 4-21 (6 mg/kg/day ip) induced a significant increase in urinary kinin excretion in norepinephrine-infused rats (1.8 mg/kg/day ip), whereas it had no effect on urinary prostaglandin E2 excretion. In contrast, MK 421 did not induce any significant changes in urinary kinin and prostaglandin E2 excretion in vasopressininfused rats (7.2 U/kg/day ip). The simultaneous administration of indomethacin (10 mg/kg/day sc), OKY 046 (12 mg/kg/day sc) or aprotinin (100, 000 units/kg/day sc) did not affect the antihypertensive effect of MK 4-21 in rats made hypertensive by chronic infusion of norepinephrine or vasopressin. The present results suggest that the hypotensive effect of MK 421 may depend on a reduced sensitivity of the vasculature to vasoconstrictor substances. In addition, it is also suggested that neither the prostaglandin-thromboxane or kallikrein-kinin systems are essential for the antihypertensive effect of MK 421 in these models of hypertension.
AB - Inhibition of angiotensin converting enzyme by MK 4-21 (6 mg/kg/day ip) induced a significant increase in urinary kinin excretion in norepinephrine-infused rats (1.8 mg/kg/day ip), whereas it had no effect on urinary prostaglandin E2 excretion. In contrast, MK 421 did not induce any significant changes in urinary kinin and prostaglandin E2 excretion in vasopressininfused rats (7.2 U/kg/day ip). The simultaneous administration of indomethacin (10 mg/kg/day sc), OKY 046 (12 mg/kg/day sc) or aprotinin (100, 000 units/kg/day sc) did not affect the antihypertensive effect of MK 4-21 in rats made hypertensive by chronic infusion of norepinephrine or vasopressin. The present results suggest that the hypotensive effect of MK 421 may depend on a reduced sensitivity of the vasculature to vasoconstrictor substances. In addition, it is also suggested that neither the prostaglandin-thromboxane or kallikrein-kinin systems are essential for the antihypertensive effect of MK 421 in these models of hypertension.
KW - ACE inhibitors
KW - Angiotensin coverting enzyme
KW - Cyclo-oxygenase inhibitor
KW - Kallikrein inhibitor
KW - Thromboxane synthetase inhibitor
UR - http://www.scopus.com/inward/record.url?scp=0023193626&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0023193626&partnerID=8YFLogxK
U2 - 10.3109/10641968709164191
DO - 10.3109/10641968709164191
M3 - Article
C2 - 2440625
AN - SCOPUS:0023193626
VL - A9
SP - 323
EP - 328
JO - Clinical and Experimental Hypertension
JF - Clinical and Experimental Hypertension
SN - 1064-1963
IS - 2-3
ER -