enalapril and 1-10-phenanthroline

Pulmonary vascular relaxant effects of the 28-amino acid atrial natriuretic peptide and atriopeptins I, II and III (21, 23 and 24 amino acid peptides, respectively) were studied in isolated blood vessels and in perfused rat lungs. In isolated tissue studies, intrapulmonary arteries were more responsive to the relaxant effects of atrial peptides than the main pulmonary artery or aorta. In perfused lung preparations, each of the four atrial peptides produced dose-dependent pulmonary vasodilation of PGF2 alpha or hypoxia-induced pulmonary vasoconstriction. Atriopeptin I was the least potent pulmonary vasodilator peptide in all studies. Pretreatment of perfused lungs with various peptidase inhibitors, including the angiotensin converting enzyme inhibitors, captopril and MK-521, the carboxypeptidase inhibitor, 1,10-phenanthroline, and the aminopeptidase inhibitor, bestatin, variably potentiated the pulmonary vasodilator activities of the atrial peptides. The results demonstrate that atrial peptides released from the right heart into the pulmonary circulation can have potent vasorelaxant effects in the pulmonary vascular bed and further suggest that upon passage through the lung atrial peptides may undergo metabolic degradation that alters their pulmonary vasodilator activities.

Topics: Aminopeptidases; Angiotensin-Converting Enzyme Inhibitors; Animals; Atrial Natriuretic Factor; Carboxypeptidases; Drug Interactions; Enalapril; In Vitro Techniques; Leucine; Lisinopril; Male; Perfusion; Phenanthrolines; Pulmonary Artery; Rats; Rats, Inbred Strains; Vasodilator Agents

Two groups of rats were pair fed, for 18 days, diets containing either 2.6 (Zn deficient) or 100 mg Zn/kg (control diet). Plasma was assayed spectrophotometrically for the activity of kininase-I and angiotensin converting enzyme (ACE) in the presence of varying concentrations of added Zn2+. Zinc deficient rats had only 76% of the activity of both kininase-I and ACE compared with zinc supplemented control rats. There was a significant linear relationship between enzyme activity and concentration of zinc in plasma for both enzymes. When zinc was added to the enzyme incubation mixture for zinc deficient rats, the activity of ACE increased by 73% and that of kininase-I by 33%. This Zn2+-stimulated increase in enzyme activity was negatively correlated with the in vivo concentration of zinc in plasma, and a plateau in enzyme activity was seen at concentrations of plasma zinc that were commensurate with normal zinc status (over 14 mumol/1). The results demonstrate that the activities of both kininase-I and ACE are dependent on the concentration of zinc in vivo and in vitro, and suggest that information concerning the concentration of zinc in plasma and assay solutions be a prerequisite solutions be a prerequisite for the use of these enzymes in the clinical diagnosis of disease states. The results also showed that the activity of ACE and kininase-I in plasma could be used for the biochemical diagnosis of a suboptimal zinc status.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Carboxypeptidases; Enalapril; Enalaprilat; Female; Lysine Carboxypeptidase; Male; Peptidyl-Dipeptidase A; Phenanthrolines; Rats; Rats, Inbred Strains; Zinc

A preparation of closed membrane vesicles derived from the longitudinal and circular smooth muscle of pig small intestine was enriched eight-fold in the activity of 5'-nucleotidase and six-fold in the activity of peptidyl dipeptidase A relative to the tissue homogenate. The membrane vesicles specifically bound [3H]bradykinin and the concentration of bradykinin required to inhibit 50% binding was 0.76 +/- 0.05 nM. This concentration was not significantly different from the corresponding concentration of lysyl-bradykinin (0.45 +/- 0.13 nM) but was less (P less than 0.05) than the concentration of methionyl-lysyl-bradykinin (1.25 +/- 0.10 nM). The concentration of des-Arg9 bradykinin (7.5 microM) required for 50% inhibition was greater than 10(3) times less than bradykinin indicating the presence of a B2-type receptor. The membrane vesicles also degraded bradykinin and the principal metabolite was identified as bradykinin. Des-Arg1 bradykinin, des-Arg9 bradykinin and bradykinin were also formed in low yield. Cleavage of the Pro7-Phe8 bond was inhibited by phosphoramidon but not by enalapril or captopril indicating that proteolytic inactivation of bradykinin in the muscle layer of the intestine is mediated through endopeptidase 24.11 ("enkephalinase") but not through peptidyl dipeptidase A ("angiotensin-converting enzyme").

Topics: 5'-Nucleotidase; Animals; Binding Sites; Bradykinin; Captopril; Cell Membrane; Drug Interactions; Enalapril; Endopeptidases; Enzyme Repression; Glycopeptides; In Vitro Techniques; Muscle, Smooth; Nucleotidases; Phenanthrolines; Swine