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1.
Miner Electrolyte Metab ; 15(3): 125-9, 1989.
Article in English | MEDLINE | ID: mdl-2542744

ABSTRACT

The effect of zinc depletion and of additional angiotensin I-converting enzyme (ACE) inhibitor treatment was studied on ACE in aortic and other tissues, in plasma and on systolic blood pressure of the rat. Zinc deprivation significantly reduced plasma zinc concentration, plasma and testicular ACE activities and blood pressure, but stimulated aortic ACE while lung values remained constant. Zinc deficiency combined with ACE inhibition further suppressed plasma ACE and stimulated the aortic enzyme earlier. Zinc repletion experiments (in vitro) suggest the existence of a feedback mechanism controlling ACE synthesis depending on plasma ACE activity.


Subject(s)
Peptidyl-Dipeptidase A/metabolism , Zinc/deficiency , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , Aorta/drug effects , Aorta/enzymology , Blood Pressure/drug effects , Body Weight/drug effects , Enalapril/analogs & derivatives , Enalapril/pharmacology , Enalaprilat , Feedback , Lung/drug effects , Lung/enzymology , Male , Peptidyl-Dipeptidase A/blood , Rats , Rats, Inbred Strains , Renin/blood , Testis/drug effects , Testis/enzymology , Zinc/physiology
2.
Circ Shock ; 21(3): 217-24, 1987.
Article in English | MEDLINE | ID: mdl-3568280

ABSTRACT

The effect of acute hemorrhage on hemodynamics and the renin-angiotensin system (RAS) was studied in eight anesthetized dogs. Stepwise blood loss to 17 +/- 6.2 ml/kg within 9 to 33 min decreased cardiac output (CO) to 42.8% of control. Mean arterial blood pressure was decreased to 35%, peripheral vascular resistance (PVR) was 1.58-fold increased, plasma renin activity (PRA) and plasma renin concentration (PRC) were increased 3.6-fold and 4.3-fold, respectively, angiotensin I (A I) concentration in plasma was 3.7-fold increased, angiotensin II (A II) was 3.8-fold increased, and A I-degrading enzyme was strongly decreased. Angiotensinogen, A I-converting enzyme, and A II-degrading enzyme activities into blood circulation were not significantly changed. The minimal blood loss to activate the RAS was 3 ml/kg. The rate of plasma active renin (PRA and PRC) increase depended on the velocity of blood withdrawn. PRA was correlated inversely to CO. PVR correlated linearly to increased plasma angiotensin concentrations. The experiments conducted demonstrate the high sensitivity and prompt activation of RAS to blood loss and suggest that RAS is involved in the regulating mechanisms of hemodynamics during acute graded hemorrhage. The stimulation of RAS supports survival of grave blood loss.


Subject(s)
Hemodynamics , Hemorrhage/physiopathology , Renin-Angiotensin System , Acute Disease , Animals , Blood Pressure , Cardiac Output , Dogs , Female , Hemorrhage/blood , Male , Vascular Resistance
3.
Biochem Pharmacol ; 35(15): 2489-93, 1986 Aug 01.
Article in English | MEDLINE | ID: mdl-3017354

ABSTRACT

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.


Subject(s)
Carboxypeptidases/blood , Lysine Carboxypeptidase/blood , Peptidyl-Dipeptidase A/blood , Zinc/pharmacology , Angiotensin-Converting Enzyme Inhibitors , Animals , Enalapril/analogs & derivatives , Enalapril/pharmacology , Enalaprilat , Female , Lysine Carboxypeptidase/antagonists & inhibitors , Male , Phenanthrolines/pharmacology , Rats , Rats, Inbred Strains , Zinc/blood
4.
Adv Exp Med Biol ; 198 Pt A: 529-36, 1986.
Article in English | MEDLINE | ID: mdl-3028073

ABSTRACT

There are indications for the existence of an intrinsic renin angiotensin system in vascular walls, which is assumed to participate in blood pressure regulation and in pathogenesis of arterial hypertension. It was evaluated if and to what extent the decapeptide angiotensin (A) I, one of the natural substrates of A I converting enzyme (ACE), is degraded by other peptidases than ACE in rat vascular tissues. A I and A II degradation was studied in arterial and venous vascular wall extracts. The activities ranged between 0.068 +/- 0.025 U and 0.044 +/- 0.025 U. The enzymes involved were biochemically characterized by determination of isoelectric points (pI), pH optima, molecular weights and by investigation of their inhibition behavior in vitro. One potent A I degrading enzyme (AIDE) was identified with pI between 3.6 and 3.9, and pH optimum at 7.75. In vitro studies revealed that AIDE activity was not blocked by the specific ACE inhibitors MK 421 or MK 422 (both 11 nMol/ml). The molecular weight of AIDE ranged between 440,000 and 457,000. The results indicate that AIDE is not identical to ACE (pI 4.2-5.0; pH optimum 8.3). AIDE was also observed in aortic smooth muscle cells cultured in vitro. AIDE decreased following bilateral nephrectomy or administration of aldosterone combined with sodium chloride loading, whereas it was elevated in spontaneously hypertensive rats (Okamoto strain). Since AIDE metabolizes A I, one of the substrates of ACE, it may indirectly affect A II formation and bradykinin inactivation as well.


Subject(s)
Aorta, Thoracic/enzymology , Endopeptidases/metabolism , Muscle, Smooth, Vascular/enzymology , Peptidyl-Dipeptidase A/metabolism , Venae Cavae/enzymology , Aldosterone/pharmacology , Animals , Female , Kinetics , Male , Rats , Rats, Inbred Strains , Renin-Angiotensin System
5.
Hypertension ; 6(3): 383-90, 1984.
Article in English | MEDLINE | ID: mdl-6329951

ABSTRACT

Investigations were performed on components of the renin-angiotensin system (RAS) in homogenate extracts of vascular tissue and aortic smooth muscle cells cultivated in vitro. Determinations of isoelectric points and pH optima indicated the existence in aortic homogenate extracts of two local angiotensin I (AI)-forming enzymes (AIFE) that were different from those of plasma, renal cortex, veins, and aortic smooth muscle cells. The pH optima for AI-converting enzyme (ACE) from vascular tissues, aortic smooth muscle cells, and plasma were in the same range (pH 8.0-8.5), and in agreement with those measured previously in other tissues. In contrast, in vitro studies with the ACE inhibitors MK-421 and MK-422 and measurement of isoelectric points suggested that aortic ACE was different from the plasma enzyme. AIFE and ACE activities were found to be elevated in spontaneously hypertensive rats (SHR). The biochemical characteristics of the enzymes investigated in the vascular tissue of SHR were not different from those of the normotensive controls. AI- and AII-degrading enzymes were found both in aortic tissue and in aortic smooth muscle cells. One potent AI-degrading enzyme different from ACE was observed in aortic tissue. A high ratio of AI/AII immunoreactivities in arterial walls suggests the availability of renin substrate, and that AI-degrading enzymes are the rate-limiting enzymes for AII formation. The results further support the concept of an intrinsic vascular RAS.


Subject(s)
Muscle, Smooth, Vascular/enzymology , Renin-Angiotensin System , Angiotensin I/biosynthesis , Angiotensin I/metabolism , Angiotensin II/metabolism , Animals , Aorta/enzymology , Female , Hydrogen-Ion Concentration , Male , Peptidyl-Dipeptidase A/metabolism , Rats , Rats, Inbred Strains
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