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)

Clonidine is an alpha-adrenergic agonist. It crosses the placenta extensively. No teratogenic effect is known in animals or in clinical practice but the question of a possible long-term behavioral teratogenicity has recently been pointed out. Clonidine does not seem to be deleterious for fetal growth, mortality and morbidity. Nothing is known about the consequences on fetal hemodynamics. The angiotensin-converting enzyme inhibitors (ACE inhibitors) captopril and enalapril act by inhibiting the formation of angiotensin II from angiotensin I. They cross the placenta. No teratogenic effect has been proved for either drug. A high rate of fetal mortality has been reported in several animal species for captopril but the available clinical data are not sufficient to assess the role of the ACE inhibitors in perinatal mortality, intrauterine growth retardation, and fetal distress in humans. The fetal hemodynamic parameters may be affected by captopril administration to the mother: blood pressure falls, plasma renin activity increases, ACE activity decreases. As for most antihypertensive drugs, available information on the consequences of clonidine and ACE inhibitors in the neonate and the infant now seem sufficient to appreciate the risk in maternal therapy. In contrast, they are still insufficient considering their known effects on fetal hemodynamics, cardiovascular adaptation, and brain tolerance, with or without hypoxia, as well as for their possible long-term adverse effects.
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PMID:Fetal effects of maternally administered clonidine and angiotensin-converting enzyme inhibitors. 269 3

The effect of clonidine, on alpha 2-agonist and antihypertensive, on the progression of chronic renal disease was studied in rats subjected to partial nephrectomy. Treatments began four weeks after the removal of approximately 70% of renal mass. Clonidine was given once daily by gavage on an increasing dose schedule of 50 micrograms/kg for 4 weeks, followed by 100 micrograms/kg for 8 weeks and finally 200 micrograms/kg for 6 weeks. Measurements of renal functions were made at 4 week-intervals during treatment. After 18 weeks, clonidine-treated rats had lower levels of plasma urea nitrogen (P less than 0.05) and plasma creatinine (P less than 0.05). Urinary protein excretion rates were lower in clonidine-treated rats while receiving 100 micrograms/kg at 8 weeks (P less than 0.05) and 200 micrograms/kg at 18 weeks (P less than 0.05). At the end of the treatment period, anesthetized clonidine-treated rats had a numerically lower mean arterial pressure (p = 0.08), but no difference in the histological ranking of light microscopic lesions (P greater than 0.10). Based on the functional data, we conclude that clonidine retards the deterioration of renal function in this model of chronic renal disease. The lack of a consistent effect of clonidine on proteinuria and no reduction in the severity of morphological damage indicates that clonidine is less effective than previously reported treatment in this model with angiotensin converting enzyme inhibition. These differences in efficacy may be related to differences in intraglomerular hemodynamic alterations and could be an important consideration in the selection of therapies for individuals with hypertension and renal insufficiency.
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PMID:Effect of clonidine on the progression of chronic renal disease in partially nephrectomized rats. 282 94

The role of central pressor mechanisms in the maintenance of blood pressure in six hypertensive patients with angiographically proven unilateral renal artery stenosis was investigated by studying the haemodynamic and hormonal responses before and after central sympathetic blockade with clonidine. To assess the dependency of blood pressure on the direct effects of angiotensin II, the same patients were studied on a separate occasion after administration of the angiotensin converting enzyme (ACE) inhibitor, captopril. There was a substantial fall in blood pressure after administration of clonidine with a smaller fall after captopril. Clonidine-induced hypotension was accompanied by a fall in cardiac output, through a reduction in the stroke volume and heart rate. Forearm vascular resistance was unchanged. There was a selective decrease in digital skin vascular resistance and plasma noradrenaline, indicating reduced sympathetic activity. Plasma renin activity and aldosterone levels did not fall. After administration of captopril, there was a fall in cardiac output due to a fall in the stroke volume but not in the heart rate. Forearm vascular resistance, digital skin vascular resistance and plasma noradrenaline were unchanged. Plasma renin activity rose and plasma aldosterone fell. We conclude that in our hypertensive patients with renal artery stenosis, clonidine lowered blood pressure by a reduction in central sympathetic activity independently of renin suppression. In these patients captopril had minimal hypotensive effects, indicating a smaller role for the direct vascular effects of angiotensin II.
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PMID:Cardiovascular and neurohormonal changes following central sympathetic blockade with clonidine in human unilateral renal artery stenosis. 307 92

In the rat model of hypertension induced by a clip on the right renal artery, sparing the left kidney, we compared the efficacity and the endocrine, renal and cardiac effects of classical therapy (CT) of hypertension (Clonidine 0.2 mg/kg and Dihydralazine 15 mg/kg in 2 daily subcutaneous injections and Furosemide 30 mg/kg/day in the drinking water), with inhibition of the angiotensin converting enzyme with a new drug, the S-9490-3 (0.5 mg/kg in one daily administration). The untreated animals (HT: n = 12) had an average systolic blood pressure (SBP) of 215 +/- 32 mmHg. After 1 month' treatment, S-9490-3 (n = 13) lowers SBP to 144 +/- 32 mmHg compared to CT (n = 12) which lowered SBP to only 172 +/- 18 mmHg. The average plasma renin concentrations of the HT animals was four times the normal value (39 +/- 33 ng/ml/h) and both treatment regimes increased it further (S-9490-3: 129 +/- 65 ng/ml/h; CT: 97 +/- 73 ng/ml/h). Angiotensin levels fell in proportion to the increase in renin concentration. Plasma aldosterone was normalised by S-9490-3 (460 +/- 320 pg/ml) but remained as high after CT (850 +/- 650 pg/ml) as in the untreated HT animals (830 +/- 260 pg/ml). Despite the Furosemide, plasma volume increased significantly in the CT group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Comparison of the cardiac, renal and endocrine effects of converting enzyme inhibition with those of a classical triple therapy in experimental renal hypertension]. 609 34

Clonidine, an antihypertensive drug that inhibits renin release and causes a water diuresis in normal animals, was tested for its ability to reduce the severity of post-ischemic acute renal failure produced in rabbits by clamping the left renal pedicle for 1 hour and removing the opposite kidney. Clonidine significantly lessened renal failure when given during, or 1 hours after, the ischemic insult in dehydrated rabbits. It was also effective when given during the ischemic insult in vasopressin-treated water-drinking rabbits but not in control water-drinking rabbits. In vasopressin-treated rabbits, clonidine lessened renal failure observed 2 days after the ischemic insult despite the fact that in the immediate postischemic period it lowered total renal blood flow, produced hypotension, and did not bring about lower plasma renin levels. Clonidine treatment resulted in less outer medullary microvascular damage (demonstrated by colloidal carbon staining), higher outer medullary blood flow 1 to 2 hours after unclamping, fewer casts, and higher creatinine clearance and free water clearance/creatinine clearance 4 to 6 hours after unclamping compared with controls. The effect of clonidine was unrelated to plasma renin activity. Clonidine did not alter plasma vasopressin concentration. Demeclocycline and lithium, two agents that blunt renal responsiveness to vasopressin, had a beneficial effect in dehydrated animals similar to that of clonidine, but the angiotensin II antagonist saralasin and the angiotensin converting enzyme inhibitor SQ20881 did not. Normal rabbits given a large dose of vasopressin in oil plus clonidine had significantly greater urine output and free water clearance and lower urine osmolality than did rabbits given vasopressin in oil alone. These results suggest that clonidine may be beneficial because it prevents ischemic microvascular injury in the renal outer medulla, an effect that may decrease tubular obstruction by lessening desquamation of damaged tubular cells or cell constituents into the tubular lumen. Clonidine may also decrease formation of obstructive hyaline casts in collecting ducts by blunting the kidney's response to vasopressin and increasing tubular fluid flow rate.
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PMID:Clonidine after renal ischemia to lessen acute renal failure and microvascular damage. 746 46