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.
N1 - Funding Information:
insufficient to inhibit cyclo-oxygenase or TX synthetase activity, since it was confirmed that urinary excretion of PGE2 or TXB a stable metatolite of TXA , was decreased with the treatmenyof indomethacin or OKY 04t by more than 60 % in preliminary experiments. Therefore, at least in rats with hypertension induced by NE or VP, lack of effects of indomethacin or OKY 046 on the antihypertensive action of MK 421 might suggest that the PG-TX system did not contribute to the blood-pressure effect of MK L21. ACKNOWLEDGMENTS This study was supported by a Grant-in-Aid for Card~i ovascular Disease from the Ministry of Health and Welfare. Japan (60-C-5). We acknowledge the -secretarial assistance of Miss J. Okazaki. REFERENCES 1. Pasujima, M., Matthews, P.G, Johnston, C.I. Regulation of uterine s m 00th mus cle bradykinin receptors by -bradykinin levels and angiotensin converting enzyme inhibitors in the rats. Clin. Exp. Pharmacol. Physiol., 1981, 8: 515-518. 2. Johnston, C.I., Pasujima, M., Clappison, B.H. The kallikrein-kinin system and angiotensin converting enzyme inhibition in hypertension. In : Angiotensin Converting Enzyme Inhibitor 8. Horovitz ZP (ed) Urban and Schwarzenberg, Baltimore-Munich, 1981, ~123-139. Abe, K., Ito, T., Sato, M., Haruyama, T., Sato, K., Omata, K., Hiwatari, M., Sakurai, Y., Imai, Y., Yoshinaga, K. Role of prostaglandin in the antihypertensive mechanism of captopril in low renin hypertension. Clin. Sci. 1980, 59: 141s-44~. Miyamoto, M., Koike, H., Ito, K., Yamazaki, M. Effects of captopril on urinary excretion of prostaglandins and electrolytes in spontaneously hypertensive rats. Eur. J. Pharmacol. 1981, 76: 187-192. Moore, T.J., Crantz, F.R., Hollenberg, N.K., Koletsky, R.J., Leboff, M.S., Swartz, S.L., Levine, L., Podolsky, S., Dluhy, R.G., Williams, G.H. Contribution of prostaglandins to the antihypertensive action of captopril in essential hypertension. Hypertension 1981, 3: 168-173. 6. Kudo, K., Abe, K., Chiba, S., Omata, K., SaC,o, K., Yasujima, M., Sato, M., Yoshinaga, K. Urinary excretion of TXB2 after angiotensin converting enzyme inhibition in hypertensive patients. Prostaglandins Leukotri. Med. 1986, 21; 77-86. 7. Yasujima, M., Abe, K., Tanno, M., Kasai, Y., Tajima, J., Seino, M., Chiba, S., Sato, K., Goto, T., Omata, K., Yoshinaga, K. Antihypertensive effect of MK 421 in rats: role of the renal kallikrein-kinin system. Hypertension 1984, 6: 229-235. 8. Yasujima, M., Abe, K., Tanno, M., Kasai, Y., Sato, K., Tajima, J., Kudo, K., Tsunoda, K., Yoshinaga, K. Renal prostaglandin E in the hypotensive mechanism of MK-421 in conscious rats. J. Hypertension 1984, 2: 623-629.
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
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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 -