Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
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Drug
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Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
Compound
Query: EC:3.4.15.1 (
ACE
)
18,300
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
To assess the role of the vascular angiotensin II-generating system in one-kidney, one clip hypertension, we determined the
angiotensin converting enzyme
activity in plasma and vascular tissues and examined the pressor response to angiotensin II, angiotensin I, and tetradecapeptide
renin
substrate in isolated mesenteric arteries from one-kidney, one clip hypertensive rats 7 and 30 days after clipping the renal artery and in mesenteric arteries from age-matched normotensive rats. Angiotensin converting enzyme activity, determined in aortic and mesenteric tissues, was significantly augmented in the hypertensive (30 days after clipping) group, whereas plasma activity was normal. The vasoconstrictor responses elicited by angiotensin I and tetradecapeptide in arteries from hypertensive rats were found to be significantly potentiated 30 days after clipping, whereas the angiotensin II responses were basically unchanged. Saralasin completely blocked the vasoconstrictor responses, whereas captopril blocked only the responses to angiotensin I without affecting the responses elicited by angiotensin II and tetradecapeptide. Enalapril, an
angiotensin converting enzyme
inhibitor given intravenously to unanesthetized rats, significantly lowered the blood pressure of hypertensive rats. The pressor responses elicited by angiotensin II, angiotensin I, and tetradecapeptide were completely inhibited by saralasin, whereas enalapril blocked only the responses of angiotensin I but not those elicited by angiotensin II and tetradecapeptide. These results indicate that local formation of angiotensin II is increased in arteries of one-kidney, one clip hypertensive rats. The data obtained with tetradecapeptide
renin
substrate suggest an important role for nonrenin proteases in vascular angiotensin II formation.
...
PMID:Increased vascular formation of angiotensin II in one-kidney, one clip hypertension. 131 51
We investigated the processing enzymes involved in the formation of circulating angiotensin-(1-7) after intravenous administration of angiotensin I to conscious spontaneously hypertensive and Wistar-Kyoto rats. Immunoreactive products, including angiotensin I, angiotensin II, and angiotensin-(1-7), were measured in arterial blood by three specific radioimmunoassays. Angiotensin I infusion (2 nmol) induced a rapid increase in immunoreactive angiotensin II and angiotensin-(1-7). Pretreatment with the
angiotensin converting enzyme
inhibitor enalaprilat (2 mg/kg) eliminated angiotensin II formation and augmented circulating levels of angiotensin I and angiotensin-(1-7) in spontaneously hypertensive and Wistar-Kyoto rats. The elevated levels of angiotensin-(1-7) in enalaprilat-treated rats were blocked by concurrent treatment with the neutral endopeptidase (EC 3.4.24.11) inhibitor SCH 39,370 (15 mg/kg) in both strains. Administration of SCH 39,370 alone decreased angiotensin-(1-7) levels in spontaneously hypertensive rats, whereas angiotensin II levels increased in both strains (p less than 0.01). Comparisons of the metabolism of angiotensin I in the two rat strains showed increased formation of angiotensin-(1-7) in spontaneously hypertensive rats not given any of the enzyme inhibitors. In addition, levels of angiotensin I were higher after administration of SCH 39,370 in hypertensive rats. These novel findings reveal that neutral endopeptidase EC 3.4.24.11 participates in the conversion of angiotensin I to angiotensin-(1-7) and in the metabolism of angiotensin II in the circulation of both spontaneously hypertensive and Wistar-Kyoto rats. Our results suggest that neutral endopeptidase EC 3.4.24.11 is a major enzymatic constituent of the circulating
renin
-angiotensin system.
...
PMID:In vivo metabolism of angiotensin I by neutral endopeptidase (EC 3.4.24.11) in spontaneously hypertensive rats. 131 52
The effect of experimentally-induced hypertension on the
angiotensin converting enzyme
(
ACE
) activity in the endothelium and smooth muscle cum adventitia of the Sprague Dawley rats was investigated. The
ACE
activity in both tissues of the 1-clip 2-kidney renovascular hypertensive rats and the deoxycorticosterone acetate/salt hypertensive rats were significantly higher than those of the normotensive control. These findings (i) support the suggestion that the 1-clip 2-kidney renovascular hypertensive rat represents a model of
renin
- and angiotensin-dependent hypertension and that the increased vascular
ACE
activity could play a role in the maintenance of hypertension (ii) provide new information regarding the association of increased vascular
ACE
activity and hypertension in the mineralocorticoid/salt treated hypertensive rats which may account for the finding by others that captopril is effective in preventing the development of hypertension in this low
renin
model of hypertension. On the other hand, the data also bring forth the possibility that the observed increase in vascular
ACE
activity could be the result of hypertension.
...
PMID:Effect of experimentally-induced hypertension on angiotensin converting enzyme activity in the aortic endothelium and smooth muscle cum adventitia of the Sprague Dawley rat. 131 37
All four components of the kallikrein-kinin system--kininogens, tissue kallikreins, kinins, and kininases--have been found in human male genital secretions. Kinins are continuously released from seminal plasma kininogens through limited proteolysis by kininogenases like tissue kallikrein from prostate and sperm acrosin. Kinins are the terminal effectors of the kallikrein-kinin system and increase sperm motility and sperm metabolism at nanomolar concentrations. Recent investigations indicate that these effects are possibly mediated by a specific sperm membrane integrated bradykinin receptor, subtype B2. The two major kininase that are present in seminal plasma are
kininase II
and neutral metallo-endopeptidase. Kininase II, which is identical with angiotensin-converting enzyme, is also involved in the
renin
-angiotensin system as it converts angiotensin I into angiotensin II and thus is the connecting enzyme of both systems. Apart from the observed effects of kinins on sperm motility, the kallikrein-kinin system is thought to be involved in the regulation of spermatogenic functions of the testis: in the rat, kallikrein activates Sertoli cell function, increases the relative number of spermatocytes and the [3H] thymidine incorporation of testicular tissue, enhances glucose-intake, and increases testicular blood flow. Clinical trials showed that systemic administration of kallikrein may be particularly useful for treatment of infertile men suffering from asthenozoospermia and/or oligozoospermia. During kallikrein therapy, the number of spermatozoa and both quantitative and qualitative sperm motility increased, and a significant improvement of the conception rate was achieved. An increased sperm number was also observed after application of the specific
kininase II
inhibitor captopril.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Possible effects of the kallikrein-kinin system on male reproductive functions. 131 46
The effect of cadmium acetate (1 mg/kg i.p.) on the
renin
angiotensin system was examined in male Sprague-Dawley rats. Blood pressure, plasma
renin
activity (PRA) and serum
angiotensin converting enzyme
(
ACE
) levels were determined in the rats. Cadmium acetate produced a hypertensive response which was not associated with elevated PRA. However,
ACE
levels in the serum were significantly decreased in the cadmium-treated group as compared with normal controls (P less than 0.01).
...
PMID:Acute effects of cadmium on the renin angiotensin system in rats. 132 27
To investigate the possible role of vascular
angiotensin converting enzyme
(
ACE
) in the development and maintenance of hypertension, we examined aortic
ACE
messenger RNA (mRNA) levels in two-kidney, one clip (2K1C) hypertensive rats. The blood pressure was increased remarkably at 4 weeks (early stage) after clipping and remained elevated at 12 weeks (chronic stage). The aorta
ACE
mRNA levels were significantly elevated in both early and chronic stages concurrently with the increases in aortic
ACE
activity and blood pressure. The plasma
renin
activity rose markedly at 4 weeks, but returned to the normal level at 12 weeks. Neither
ACE
activity in the lung and plasma, nor
ACE
mRNA level in the lung was altered at either stage. The aorta and liver angiotensinogen mRNA levels and renal
renin
mRNA level were increased at 4 weeks but decreased at 12 weeks. These results indicate that the acceleration of all components in the
renin
-angiotensin system may contribute to the development of 2K1C hypertension in the early stage. In the chronic stage, the increased vascular
ACE
induced by the elevated
ACE
mRNA levels in the aorta may play the primary role in the acceleration of local angiotensin II formation and thus may sustain the hypertension.
...
PMID:Increase of angiotensin converting enzyme gene expression in the hypertensive aorta. 132 65
The involvement of the circulating and local
renin
-angiotensin system in atherosclerotic process has been hypothesized on the basis of experimental data showing presence and specific actions of the components of this system in the vascular wall. In particular, angiotensin II may participate in well known events in atherogenesis as the control of smooth muscle cell growth and proliferation. Recent studies have shown an effect of
angiotensin converting enzyme
(
ACE
) inhibition on the development of atherosclerosis in animal models. Captopril and cilazapril prevent myointimal proliferation after vascular injury in rat. Captopril reduces aortic cholesterol content and percentage intimal aortic surface covered by lesions in Watanabe heritable hyperlipidemic rabbits. Captopril also significantly reduces the progression of carotid and coronary lesions in monkeys fed a high cholesterol diet. In addition, a role for converting enzyme inhibitors in reducing aortic and microvascular growth either in hypertensive or normotensive rats has been demonstrated. It is possible that
ACE
-inhibitors prevent angiotensin II-induced vascular proliferation and thereby suppress the development of atherosclerosis in animals. It is also conceivable that the blood pressure effects of
ACE
-inhibitors could play a role in the antiatherosclerotic effect shown by these drugs, even though this explanation cannot be addressed by studies dealing with normotensive animals. Then, other mechanisms could be involved, including hypothesized effects of blockade of the
renin
-angiotensin system on sympathetic nervous system activity, regulation of vascular growth factors and insulin sensitivity. The clinical significance of these experimental findings is unknown.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:ACE-inhibitors and atherosclerosis. 132 85
To evaluate the role of certain plasma biosubstances on the development of pulmonary hypertension and shock during severe hypoxia, hypercapnia and acidosis, plasma
renin
activity (PRA), angiotensin II (ATII),
angiotensin converting enzyme
(
ACE
), TXB2 and 6-Keto-PGF1 alpha (the stable metabolites of TXA2 and PGI2) were assayed in blood from pulmonary artery and aorta in seven pigs. Pulmonary arterial pressure (PAP) was monitored via Swan-Ganz catheter. During hypoxic and hypercapnic ventilation, PaO2 dropped to 4.7 kPa, PaCO2 rose to 21.1 kPa, pH dropped to 6.82, PAP increased from 2.43 +/- 0.06 to 4.46 +/- 0.45 kPa when acidotic shock developed (all P less than 0.05). Meanwhile ATII levels rose (all P less than 0.05). PRA significantly increased during acidotic shock as compared with normal ventilation (P less than 0.02).
ACE
dropped significantly (P less than 0.05), TXB2 and 6-keto-PGF1 alpha showed no significant change before and after hypoxic and hypercapnic ventilation.
...
PMID:[Plasma renin activity, angiotensin II, angiotensin converting enzyme, thromboxane A2 and prostacyclin I2 levels in pigs with severe hypoxia and hypercapnea and acidosis shock]. 132 48
We report here the alterations of serum angiotensin-converting enzyme activity (S-ACE) and of active
renin
plasma concentrations (ARPC) in 41 insulin-dependent diabetes mellitus (IDDM) patients compared with those of 26 control subjects. The IDDM patients had S-
ACE
activity (54 +/- 16 I.E.) in the upper normal range (controls, 39 +/- 7). When the patients were subclassified according to their diabetic complications, a significant increase of S-
ACE
within the IDDM group compared to the controls was observed in patients with nephropathy (68 +/- 13, P less than 0.001) with persistent proteinuria and with retinopathy (63 +/- 14, P less than 0.001). A significant correlation was found between proteinuria and S-
ACE
(r = 0.98, P less than 0.001) and between retinopathy and S-
ACE
levels (r = 64, P less than 0.001). No correlation between blood pressure and S-
ACE
or between blood glucose and S-
ACE
was observed. The ARPC were within the normal range in the IDDM (21 +/- 9 ng/l) and in control (19 +/- 3) groups. No correlations between ARPC and blood pressure or blood glucose or the degree of diabetic complications were registered. These data show that S-
ACE
activity is elevated in IDDM patients with nephropathy-proteinuria and/or with retinopathy and the circulating
renin
may not represent the renal
renin
-angiotensin vascular system.
...
PMID:Serum angiotensin-converting enzyme activity and active renin plasma concentrations in insulin-dependent diabetes mellitus. 133 Apr 63
Effect of oestradiol was studied on the
angiotensin converting enzyme
(
ACE
)--a component of
renin
angiotensin system, in oviduct of immature quails of 15 days of age.
ACE
was studied in whole oviduct, magnum, shell gland and the glandular epithelium of magnum and shell gland. It was found that whole oviduct had a significantly higher level of
ACE
in control than those treated with exogenous estrogen at three dose levels (200, 400 or 600 micrograms).
ACE
contents of whole muscle and glandular epithelium did not differ but magnum had higher
ACE
level than the shell gland. Results are explained on the basis of functional role of oviductal parts.
...
PMID:Effect of estrogen on angiotensin converting enzyme in immature quail oviduct. 133 45
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