Effect of DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid on the blood pressure response to vasoactive substances

Abstract

The importance of kininase I (carboxypeptidase N) in the catabolism of circulating kinins is not known. DL-2-Mercaptomethyl-3-guanidinoethylthiopropanoic acid (MGTA) has been reported to be an inhibitor of kininase I both in vitro and in vivo. In order to evaluate the possible role of kininase I in the in vivo inactivation of bradykinin, the authors studied the blood pressure responses of pentobarbital-anesthetized rats to bradykinin before and after the i.v. administration of MGTA (a 10-mg/kg bolus followed by 1 mg/kg/min continuous infusion). MGTA potentiated bradykinin-induced hypotension. The specificity of MGTA for kininase I was tested using other peptide and nonpeptide vasoactive substances. MGTA potentiated the hypertension due to angiotensin I, angiotensin II and vasopressin, but it did not affect the response to phenylephrine. On the other hand, MGTA did not potentiate the hypotensive action of acetylcholine, but it did potentiate that of sodium nitroprusside. The potentiation of bradykinin-induced hypotension is compatible with inhibition of kininase I by MGTA. The data suggest, however, that MGTA is not selective for any enzyme that inactivates kinins, inasmuch as other peptides and nonpeptide vasoactive substances are also potentiated.