Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hypothesis that vasopressin participates in cardiovascular adaptation to sodium depletion was examined in male Sprague-Dawley rats studied after 6 days (n = 28) or 4 weeks (n = 28) of low sodium diet. Blood pressure was similar on the two diets but heart rate, water intake and urine volume were all significantly greater at 4 weeks. Animals were randomly assigned to four acute treatment groups: controls, vasopressin pressor antagonist, d(CH2)5Tyr(Me)AVP (AVPA, 10 micrograms/kg); angiotensin converting enzyme (ACE) inhibitor, enalaprilic acid (150 micrograms/kg); combined ACE inhibitor and AVPA. Cardiac output and blood flow distribution were measured using labelled microspheres. Blood pressure, cardiac output and blood flow distribution were unchanged after AVPA alone. Angiotensin converting enzyme inhibition and ACE inhibitor plus AVPA produced similar falls in mean blood pressure at 6 days (-12 +/- 1, -14 +/- 3 mmHg) and 4 weeks (-11 +/- 2, -16 +/- 2 mmHg) due to parallel falls in peripheral resistance. Angiotensin converting enzyme inhibition was associated with selective increases in renal and mesenteric blood flow. Renal blood flow increased further after combined blockade at 6 days (ACE inhibitor 9.68 +/- 0.71; ACE inhibitor plus AVPA 11.92 +/- 0.73 ml/min per g, P < 0.05) but not at 4 weeks (ACE inhibitor 11.15 +/- 0.23; ACE inhibitor plus AVPA 10.76 +/- 0.78 ml/min per g). Vasopressin appears to contribute to early but not late cardiovascular adaptation to sodium depletion. A specific effect on the renal vascular bed is only revealed after removal of the dominant effect of angiotensin II (ANG II).
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PMID:Role of vasopressin in cardiovascular adaptation to sodium depletion in the conscious rat. 285 60

The contribution of vasopressin and angiotensin II to the maintenance of blood pressure after short-term autonomic blockade was investigated in conscious Long-Evans and Brattleboro (vasopressin-deficient; hereditary diabetes insipidus) rats. After short-term autonomic blockade by atropine (1 mg/kg), propranolol (5 mg/kg), and pentolinium (5 mg/kg and 10 mg/kg/hr), the fall in blood pressure was significantly greater in Brattleboro rats than in Long-Evans rats (48 +/- 3 vs 32 +/- 2 mm Hg; p less than 0.01). Administration of the vasopressin vascular receptor antagonist D(CH2)5Tyr-(Me)AVP (2 micrograms/kg) caused further blood pressure decreases only in Long-Evans rats, so that the final blood pressure in both groups was identical. Administration of enalaprilat (10 mg/kg), an angiotensin converting enzyme inhibitor, further reduced blood pressure in both strains. When enalaprilat was given first after autonomic blockade, it reduced blood pressure in Brattleboro rats but not in Long-Evans rats. Administration of the vasopressin antagonist after enalaprilat further reduced blood pressure only in Long-Evans rats. The fall in blood pressure following vasopressin blockade was greater than that occurring after angiotensin converting enzyme inhibition (14 +/- 1 vs 6 +/- 1 mm Hg; p less than 0.05) in autonomic blockade Long-Evans rats. Plasma levels of vasopressin in Long-Evans rats increased markedly after short-term autonomic blockade, whereas plasma renin and angiotensin II levels were unchanged. Plasma angiotensin II levels were increased by the vasopressin antagonist and decreased by enalaprilat. We conclude that, due to sympathetic nervous system blockade and consequent blunting of renal renin release, vasopressin has a greater capacity than the renin-angiotensin system for maintaining blood pressure after short-term autonomic blockade.
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PMID:The contribution of vasopressin and angiotensin to the maintenance of blood pressure after autonomic blockade. 298 71

Lesions of the ventrolateral medulla of the rabbit, coinciding with the A1 noradrenaline cell bodies (A1 lesions) produced fortyfold increases in the plasma levels of vasopressin and adrenaline, a twofold increase in plasma noradrenaline and a substantial increase in plasma renin activity. These increases accompanied the hypertension and bradycardia that follow A1 lesions. The vasoconstriction and hypertension were completely abolished by phentolamine, an alpha-adrenoceptor antagonist, when it was administered before lesions and were markedly reduced when it was given after lesions. On the other hand, administration of an antagonist to the vasoconstrictor action of vasopressin (d(CH2)5Tyr(Me)AVP) or an angiotensin converting enzyme inhibitor had little effect. Prior removal of the adrenal glands prevented any rise in plasma adrenaline levels but had no effect on the pressure response to subsequent A1 lesions. These results indicate that the vasoconstriction and hypertension were predominantly mediated by alpha-adrenoceptor stimulation, acting mainly through sympathetic vasoconstrictor nerves. The fall in heart rate following A1 lesions was approximately halved by pretreatment either with d(CH2)5Tyr(Me)AVP alone, or by blockade of the vagus and sympathetic with scopolamine and propranolol; it was completely abolished by combined pretreatment with all three agents. The experiments show that vasopressin release makes a major contribution to the bradycardia acting at least in part through mechanisms that are independent of cardiac vagal or sympathetic nerves.
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PMID:The mechanism of hypertension and bradycardia following lesions of the caudal ventrolateral medulla in the rabbit: the role of sympathetic nerves, circulating adrenaline, vasopressin and renin. 299 15

Experiments were carried out in male Sprague-Dawley rats. 3'-end digoxigenin-labeled 26 bp oligonucliotide probe was used to detect the vasopressin (AVP) mRNA in the hypothalamus. Dot blotting technique was used in the investigation of AVP gene transcription level. The results showed that continuous intracerebroventricular administration (i.c.v.) of angiotensin II at a rate of 0.2 nmol/h for 2 days by using a miniosmotic pump resulted in a significant increase in daily water intake. An increase of AVP gene transcription level in the hypothalamus was also observed, but statistically insignificant. When daily water intake was limited (25 ml/d), continuous i.c.v. infusion of ANG II caused a significant increase in hypothalamic AVP gene transcription. It was also observed that hypothalamic AVP gene transcription level increased after salt loading and dehydration. However, intraperitoneal application of angiotensin converting enzyme inhibitor captopril (5 mg/(kg.d)) or i.c.v. nonpeptide angiotensin II receptor antagonist Dup753 (0.9 nmol/h) did not attenuate the increase of AVP gene transcription level induced by salt loading or dehydration. It is therefore suggested that the administration of ANG II enhances AVP gene transcription in the hypothalamus, especially when water intake is limited. However, this increase does not involve the participation of endogenous ANG II.
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PMID:[Effect of angiotensin II on vasopressin gene transcription in the hypothalamus of rats]. 748 79

The influential studies by Hostetter and associates [103] as well as by others in the last decade have firmly established the association between adaptive increases in renal hemodynamics as well as tubular reabsorption and the progression of renal disease. Many different vasoactive hormones may be involved in such regulatory processes. On the other hand, many investigators have observed that compensatory renal growth, although initially helping to restore functional renal tissue, may be rather harmful in the long-term for renal function, even in the absence of concomitant hemodynamic changes. These apparently separate areas of renal pathophysiology have become united by the identification of the growth regulatory properties of many vasoactive substances. Thus, a perturbation of vasoconstrictors and vasodilatory substances may not only influence vascular tone, glomerular filtration rate and renal plasma flow but also the growth regulation of distinct populations of cells along the nephron. As a generalization, it appears that vasoconstrictors stimulate growth of renal cells (mitogenesis and hypertrophy), whereas vasodilators inhibit the growth response. It can be speculated that similar effects of different hormones may depend on the activation of common second messenger pathway, e.g. the ANG-II-, AVP-, ET-induced mesangial proliferation through the phosphorylation of a common set of target proteins, or the antimitogenic effects of ANP, EDRF and PGE2 through an increase in intracellular cGMP. However, the majority of the growth regulatory effects of vasoactive substances have been studied in relatively artificial cell culture systems. Nevertheless, the well-documented protective effects of ACE inhibitors on renal function in several models include effects on renal growth. The rapid development of new vasoactive drugs like the recently introduced nonpeptide ANG II receptor antagonists may also offer an opportunity to influence renal growth [104]. The mechanisms of the progression of renal disease have become fascinatingly complex, and the next years will most likely witness major achievements in the elucidation of chronic renal pathophysiology on both cellular and molecular levels.
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PMID:Vasoactive substances as regulators of renal growth. 808 63

CHF is a common, complex and life-threatening clinical syndrome. It is widely accepted that enhanced peripheral vascular tone plays a major role in the pathophysiology of CHF. Increased activity of the sympathetic nervous system is one of the most important factors responsible for the increased afterload in CHF. This increase in sympathetic activity occurs early in the course of development of CHF. Efferent sympathetic activity is distributed in a non-uniform way in CHF, with significant increases to the heart and kidney but normal activity to some other organs such as the lung. Increased renal sympathetic activity contributes significantly to altered neural haemodynamics, sodium and water retention, and modulation of the actions of other vasoactive hormones. The regional alteration in sympathetic activity may be largely responsible for the changes in resting regional blood flow to different organs in CHF and the maldistribution of blood flow that occurs during the stress of exercise. Disordered function of cardiovascular reflexes is observed in CHF and may contribute to disordered sympathetic function. In CHF there are significant interactions between the sympathetic nervous system and other humoral systems such as the renin-angiotensin system, AVP, ANP, endothelin and renal DA. The various drugs used in the treatment of CHF have different effects on sympathetic activity: digitalis and ACE inhibitors tend to suppress activity while diuretics may have the opposite effect. Following cardiac transplantation, there is a prompt return of sympathetic function towards normal, although the heart may remain significantly denervated for a long time, with gradual reinnervation. Cyclosporin therapy tends to increase sympathetic activity and this may contribute to post-transplant hypertension.
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PMID:Sympathetic dysfunction in heart failure. 848 86

The purpose of this study was to evaluate the effects of early administration and removal of the ACE inhibitor, captopril (CAP) on the plasma ACE activity, AVP levels, and mean arterial pressure (MAP) in groups of rats, control and CAP treated SHR and WKY (SHR, WKY SHRCAP, WKYCAP, respectively and in SHR taken off CAP (OFFCAP) and their progeny (2nd generation, 2ndG). Plasma ACE activity in SHRCAP (54.8 +/- 2.1 mU/ml/min) was significantly greater than in SHR (25.96 +/- 0.34 mU/ml/min) and their offspring (OFFCAP, 26.32 +/- 2.71 and 2ndG, 17.62 +/- 2.47 mU/ml/min, P < 0.001, respectively). Plasma level of AVP in SHR (14.18 +/- 0.98 pg/ml) were greater than in SHRCAP (9.1 +/- 1.01 pg/ml, P < 0.01). A decrease in plasma AVP levels were also noted in OFFCAP (10.48 +/- 0.51 pg/ml) and their offspring 2ndG (10.34 +/- 0.46 pg/ml). Our results did not show a relationship between plasma ACE activity and blood pressure reduction. However, treatment of SHR with captopril produced a decrease in plasma AVP levels which may participate in its antihypertensive mechanism of action.
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PMID:Effects of early captopril treatment and its removal on plasma angiotensin converting enzyme (ACE) activity and arginine vasopressin in hypertensive rats (SHR) and normotensive rats (WKY). 886 1

The effects of a 3-day water deprivation were studied in adult female rats in order to know what are the different zones of the adrenal gland and the hormonal factors involved in the growth and the activity of the adrenal gland. Water deprivation significantly increased plasma renin activity (PRA), plasma Angiotensin II (AII), vasopressin (AVP), epinephrine, aldosterone and corticosterone concentrations but did not modify the plasma adrenocorticotropin hormone (ACTH) level. Water deprivation significantly increased the absolute weight of the adrenal capsule containing the zona glomerulosa without modification of the density of cells per area unit suggesting that the growth of the adrenal capsule was due to a cell hyperplasia of the zona glomerulosa. Water deprivation significantly increased the density of AII type 1 (AT(1)) receptors in the adrenal capsule but did not modify the density of AII type 2 (AT(2)) receptors in the adrenal capsule and core containing the zona fasciculata, the zona reticularis and the medulla. The treatment of dehydrated female rats with captopril, which inhibits the angiotensin converting enzyme (ACE) in order to block the production of AII, significantly decreased the absolute weight of the adrenal capsule, plasma aldosterone and the density of AT(1) receptors in the adrenal capsule. The concentration of corticosterone in the plasma, the density of AT(2) receptors and the density of cells per unit area in the zona glomerulosa of the adrenal capsule were not affected by captopril-treatment. In conclusion, these results suggest that AII seems to be the main factor involved in the stimulation of the growth and the secretion of aldosterone by the adrenal capsule containing the zona glomerulosa during water deprivation. The low level of plasma ACTH is not involved in the growth of the adrenal gland but is probably responsible for the secretion of corticosterone by the zona fasciculata.
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PMID:Trophic and steroidogenic effects of water deprivation on the adrenal gland of the adult female rat. 1257 7

Diuretics continue to be a mainstay in patients with CHF. Conventional diuretic therapy is associated, however, with potentially deleterious neurohumoral activation and renal impairment. It is not known to what extent these neurohumoral effects are offset by concurrent therapy with ACE-I, beta-blockers, and other agents. In the past, there was no alternative to conventional diuretic therapy, so their potential for adverse outcome in the long term could not be assessed. Enhancement of the natriuretic peptide system could provide us with a better strategy to treat sodium and water retention. In a unique way, the natriuretic peptides combine several of the beneficial actions of the other diuretics, but without the associated cost. Natriuretic peptides, like conventional diuretics, are natriuretic and diuretic. There are important differences, however. First, unlike conventional diuretics, NPs do not activate RAAS. Activation of this system is associated with progression of CHF. Second, NPs inhibit the sympathetic nervous system, the activation of which is associated with heart failure progression, myocyte necrosis and apoptosis, and arrhythmias. Third, unlike conventional diuretics that lead to a decrease in GFR by reflex mechanisms. NPs maintain or even improve GFR. We now appreciate that some "old" drugs may be beneficial to CHF patients in a new way, as is the case with spironolactone. The survival benefit of this aldosterone antagonist is clear: its usefulness, however, may be more a result of both its antifibrotic actions in addition to its tradional role as a potassium-sparing and natriuretic agent. It is hoped that the SARAs will provide the same survival benefit, but with fewer of the sex-steroid side effects. In addition, AVP-receptor antagonists may become useful tools in the treatment of patients with hyponatremia. Likewise, the A1 AR antagonists may find a role in the CHF armamentarium by providing good diuresis and natriuresis while at the same time maintaining GFR through inhibition of TGF. Many questions remain unanswered, and studies are needed to demonstrate that the positive results seen in basic research translate into improved morbidity and mortality.
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PMID:Revisiting salt and water retention: new diuretics, aquaretics, and natriuretics. 1269 35

Nephrotic syndrome is common in immunoglobulin light-chain (AL) amyloidosis and successful therapy may pose a challenge. We report the case of a 63-year-old patient with severe nephrotic syndrome due to primary renal AL-amyloidosis with well-preserved renal function at first presentation. Therapy with high dose steroids, loop diuretics, and ACE-inhibitors did not affect his proteinuria and he was seriously disabled because of symptomatic orthostatic hypotension and anasarca. With the patient's informed consent, medical nephrectomy was tried with nonsteroidal-anti-inflammatory drugs (NSAIDs), cyclosporine, and aminoglycosides, with significant deterioration of his renal function, but without relevant effect on his proteinuria. Despite adequate anticoagulation life threatening thrombotic and bleeding complications occurred. Total renal ablation was finally achieved using an Amplatzer vascular plug Typ IV (AVP 4) with a self-expanding Nitinol mesh design, which was placed in both main renal arteries in the same intervention. The patient became completely anuric, protein loss stopped, and serum albumin slowly rose to normal levels. The patient's clinical condition dramatically improved and he regained his full mobility at the price of a lifelong renal replacement therapy. To our knowledge, this is the first reported usage of such a vascular occluder in the setting of refractory nephrotic syndrome with normal kidney function at the time of first presentation.
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PMID:Radiologically Guided Renal Artery Embolization with an Amplatzer Vascular Plug as a Rescue Therapy for Refractory Nephrotic Syndrome in AL-Amyloidosis. 3088 53


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