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 hypotensive efficacy of (S)-1-[6-amino-2[[hydroxy(4-phenylbutyl) phosphinyl]oxy]-1-oxohexyl]-L-proline (SQ 29,852), a phosphorus-containing novel angiotensin converting enzyme inhibitor (ACEI) was examined in conscious two-kidney, one-clip Goldblatt hypertensive dogs. The acute hypotensive effect of SQ 29 852 was compared with that of captopril or enalapril at 3 mg/kg, p.o., for each, and the potencies were ranked as follows, enalapril greater than SQ 29,852 greater than captopril. On the other hand, the hypotension caused by repetitive dosing with SQ 29,852 (3 mg/kg, p.o./d for 7 d followed by another 7-d treatment with 10 mg/kg, p.o./d) was somewhat more marked than that by enalapril at the same dosage. Blood urea nitrogen (BUN) increased in all the animals given enalapril, while that in all of the SQ 29,852-treated animals did not increase. These results indicate that SQ 29,852 is a potent, and long-lasting ACEI with a possible low incidence of side effects.
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PMID:Hypotensive effect of a phosphorus-containing novel angiotensin converting enzyme inhibitor, (S)-1-[6-amino-2[[hydroxy(4-phenylbutyl)phosphinyl] oxy]-1-oxohexyl]-L-proline (SQ 29,852) in conscious hypertensive dogs. 143 66

Blood pressure (BP) was recorded directly and automatically by a microcomputer aid system for 48 h in normotensive and Goldblatt hypertensive goats. By population-mean cosinor fitting, significant circadian rhythms were found for SBP and DBP in both groups of goats. The BP during nighttime was higher than that during daytime in our goats. An angiotensin converting enzyme inhibitor, captopril, was given to hypertensive goats with usual schedule of drug administration (25mg, t.i.d) or form of chronotherapy (62.5 mg, given before the acrophase of BP, q.n). BP significantly decreased throughout the whole day in both treated groups. But there was no statistical difference of cosinor parameters between the effects of BP in these two groups. BP could be decreased by the method of chronotherapy with less amount of drug and less frequency of drug administration.
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PMID:[Circadian rhythm of blood pressure in renovascular hypertensive goats treated with captopril]. 145 52

In order to study why the diagnostic sensitivity of 123I-hippurate renography for a renal artery stenosis is improved by angiotensin converting enzyme (ACE-) inhibition we used the model of the conscious chronically instrumented two-kidney, one-clip Goldblatt hypertensive dog. Urine flow (UV), renal blood flow (RBF), glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured (with constant infusion of 125I-iothalamate and 131I-hippurate, respectively) for both kidneys separately before and after a bolus injection of a mild unilateral renal artery stenosis (approximately 30% reduction of RBF). During ACE-inhibition, there were remarkable falls in poststenotic GFR (from 37 +/- 5 to 4 +/- 2 ml/min, p less than 0.05), ERPF (from 111 +/- 13 to 21 +/- 10 ml/min, p less than 0.05) and UV (from 0.86 +/- 0.15 to 0.075 +/- 0.045 ml/min, p less than 0.05), whereas RBF of the poststenotic kidney slightly increased (from 193 +/- 18 to 237 +/- 27 ml/min, p less than 0.05). The concentration of hippurate and thalamate in the blood remained remarkably constant while the excretion of the tracers by the poststenotic kidney diminished and renal retention of 123I-hippurate was seen on the renogram. In 2 dogs, the experiments were repeated during mannitol infusion. In that situation, there was a much smaller decrease of poststenotic UV and GFR whereas ERPF even showed a small increase comparable to the RBF changes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in renal function induced by ACE-inhibition in the conscious two-kidney, one-clip Goldblatt hypertensive dog. 155 9

The well established differential pulmonary handling of angiotensins I and II indicates the possibility that vascular receptors for the deca- and octa-peptides do not necessarily involve common sites in the renal vasculature either. Experimental findings involving haemodynamic changes within the kidney in anaesthetised and conscious sheep, with utilization of the angiotensins, and also of noradrenaline, are briefly presented; the implications of the intra-renal water and creatinine transfers are discussed, especially as they concern the possible location of angiotensin receptors in the renal blood vessels. Other aspects of the relationships between the peptides are also taken into account particularly with regard to a postulated angiotensin I [NaCl] dependent peritubular capillary antidiuretic action, angiotensin converting enzyme inhibition, Goldblatt clamp induced hypertension and blood flow through the hind-limbs.
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PMID:Receptors for angiotensins I and II: their relevance to renal haemodynamics, blood pressure control and hind-limb blood flow. 176 16

We measured the concentrations of three principal products of the renin-angiotensin system and seven of their metabolites in the plasma of anesthetized normal dogs and in dogs 24 hours after bilateral nephrectomy. The levels of the angiotensin peptides were measured by high-performance liquid chromatography combined with radioimmunoassay using three specific antibodies that recognized different epitotes in the sequences of angiotensin I, angiotensin II, and angiotensin-(1-7). The analysis revealed that angiotensin-(1-7) is present in the plasma of intact (4.9 +/- 2.2 fmol/ml) and nephrectomized (0.5 +/- 0.5 fmol/ml) dogs. An intravenous injection of purified hog renin (0.01 Goldblatt unit/kg) increased plasma levels of angiotensin I, angiotensin II, and angiotensin-(1-7) both before and after nephrectomy. These changes were associated with parallel increases in the concentrations of fragments of the three parent peptides. Administration of MK-422 led to the disappearance of circulating angiotensin II and its fragments both before and after a second injection of the same dose of renin. In contrast, MK-422 augmented the plasma levels of both angiotensin I and angiotensin-(1-7). The concentrations of these two peptides, but not the blood pressure, were again augmented by a second injection of renin given after blockade of converting enzyme. These effects were observed both before and after bilateral nephrectomy. These findings show that angiotensin-(1-7) circulates in the blood of normal and nephrectomized dogs. In addition, we found that angiotensin-(1-7) is generated in the blood from the cleavage of angiotensin I through a pathway independent of converting enzyme (EC 3.4.15.1).
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PMID:Angiotensin-(1-7). A member of circulating angiotensin peptides. 184 40

Morphologic evidence from patients with essential hypertension and Goldblatt-type hypertension reveals a subpopulation of narrowed afferent arterioles to ischemic nephrons. These ischemic nephrons, responding individually to their perception of underperfusion, secrete renin. In response, the normal nephrons are in adaptive natriuresis and have appropriately shut off their renin production. Nevertheless, they are affected adversely by the discordant renin-angiotensin II arising from the ischemic nephrons' presence, which exerts an unwanted sodium-retaining effect on the proximal tubules of the adapting nephrons. The end result is elevated blood pressure from too much sodium retention for the level of renin activity, that is, an abnormal renin-sodium product. Thus, "normal" renin levels in a hypertensive individual are abnormal because healthy kidneys shut off renin production entirely when blood pressure rises. This construction explains why angiotensin converting enzyme inhibition often corrects "normal" renin hypertension. Although such hypertension may be partly sodium-mediated as a consequence of inappropriate sodium retention by the normal and ischemic nephrons, the source of the problem lies in the renin production from ischemic nephrons. The correct treatment, then, is an antirenin therapy designed to block renin synthesis or secretion or angiotensin II formation or action. In view of modern studies suggesting that renin excesses also correlate with an increased risk of heart attack and stroke, the role of antirenin and antiangiotensin agents in treatment assumes additional relevance.
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PMID:Discordant nephron function. A pathogenic factor in hypertension and its vascular complications of stroke and heart attack. 200 43

This study was undertaken to verify the activity of plasma kininases in hypertension. Male Wistar rats (WIS) were used and three models of experimental hypertension were studied: spontaneously hypertensive rats (SHR), renal hypertensive rats, made according to the method of Goldblatt, DOCA-salt hypertensive rats. Normal Wistar rats, nephrectomized rats and sodium-loaded rats were used as control groups. Plasma from these animals was used to evaluate the kininase activities: kininase II activity (KII) was measured by the hydrolysis of hippuryl-L-histidyl-L-leucine (HHL); kininase I activity (KI) was measured by the hydrolysis of hippuryl-L-arginine (HLA) (CN1 activity) and of hippuryl-L-lysine (HLL) (CN2 activity). The three enzyme activities were characterized by their kinetic constants and the inhibitory pattern of various inhibitors. In normal WIS rats, hydrolysis of HHL proceeds with a Km of 2.55 +/- 0.22 mM and at a Vmax of 0.357 +/- 0.017 mumol/min/ml; the enzyme is inhibited by EDTA, 0-phenanthroline and captopril. HLA has a Km of 6.93 +/- 0.32 mM and a Vmax of 0.748 +/- 0.019 mumol/min/ml while the Km and Vmax values of HLL are 35.8 +/- 1.52 mM and 13.11 +/- 0.40 mumol/min/ml. The hydrolysis of both substrates is inhibited by EDTA, 0-phenanthroline and MERGETPA. KII activity is decreased in WKY and SHR rats (Vmax = 0.241 +/- 0.014 and 0.262 +/- 0.011 mumol/min/ml, respectively). In renal hypertensive rats and DOCA-salt hypertensive rats, the KII activity remained unchanged. CN1 activity was increased in 1K, 1C hypertensive animals (Vmax = 0.866 +/- 0.221 mumol/min/ml) and in DOCA-salt hypertensive rats (Vmax = 1.119 +/- 0.049 mumol/min/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Activity of plasma kininase I and kininase II in hypertensive rats]. 217 85

Pressor response to exogenous angiotensins was investigated in rats. Two-kidney Goldblatt hypertensive rats (GHR) and sodium-deficient normotensive rats (SDR), as well as normal rats, (NR) were used. Various amounts of angiotensin I (Ang I) or angiotensin (Ang II) were administered intravenously by constant infusion, with or without pretreatment with angiotensin converting enzyme (ACE) inhibitor, and the pressor response was determined. Captopril was used as the ACE inhibitor. From the data obtained, a simple kinetic model for the renin-angiotensin system was constructed. The model was based on a linear compartment model with the following assumptions; (a) there are compartments in respect to Ang I and II in the body; (b) in the steady-state condition, Ang I is produced at a constant rate; (c) a part of Ang I is converted to Ang II by a first-order rate process; (d) Ang I and II are eliminated from the respective compartments by first-order rate processes and (e) the relationship between mean arterial blood pressure and the amount of Ang II in the body can be described by Hill's equation with a baseline effect. Then the pressor response to angiotensins in GHR, SDR or NR was fitted to the model. The result indicated that the pressor response to Ang I or Ang II can be described by the present model. The model parameters obtained were consistent with the actual physiological parameters of rats.
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PMID:Kinetic studies of the pharmacologic response to captopril in rats. I. Role of the renin-angiotensin system. 254 16

The effect of captopril on the mean arterial blood pressure was studied in rats. Two different disease-state rats, namely the sodium-deficient rat (SDR) and the two-kidney-one-clip Goldblatt hypertensive rat (GHR), as well as normotensive rats (NR), were used. After i.v. bolus administration of captopril to each rat, the time course of plasma angiotensin converting enzyme (ACE) activity and mean arterial blood pressure were determined. In a different experiment, the effect of captopril on the plasma ACE activity in vitro was determined. Captopril inhibited the plasma ACE activity in a concentration-dependent manner and the relationship between concentration of captopril and inhibition of plasma ACE activity in vitro was reasonably described by a Langmuir-type equation. Then, plasma concentrations of captopril after i.v. administration were estimated by means of this equation. The estimated plasma concentration of captopril followed a double exponential equation. From the data obtained, a kinetic model including the renin-angiotensin system and pharmacokinetics of captopril was constructed under the following assumptions; (1) the hypotensive effect of captopril is solely attributable to the reduction of angiotensin II level in the body, (2) the production rate of angiotensin II is proportional to the total ACE activity and (3) plasma ACE activity reflects the total ACE activity in the body. Then, the effect of captopril on the mean arterial blood pressure in each type of rat was calculated. The results indicated that the hypotensive effect of captopril in NR was reasonably described by the model. However, the hypotensive effect of captopril in both GHR and SDR could not be well described by the model.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Kinetic studies of the pharmacologic response to captopril in rats. II. Hypotensive effect and plasma angiotensin converting enzyme activity. 254 17

MK-0521 and captopril were orally administered to acute (6 to 8 days after unilateral renal artery constriction) and chronic (2 to 2.5 months after the constriction) 2-kidney Goldblatt hypertensive dogs for 7 to 21 days. MK-0521 lowered the blood pressure to similar extents in the acute and chronic stages of hypertension. The antihypertensive effect of MK-0521 was dose-dependent and persistent even after its cessation. Captopril also produced an antihypertensive effect, although the effect in the chronic stage of hypertension was less prominent than that in the acute stage of hypertension. MK-0521 was more inhibitory on the renin-angiotensin system than captopril. In the acute stage of hypertension, the dogs treated with MK-0521 had increased angiotensin converting enzyme (ACE) activity, while they had decreased plasma angiotensin II level and elevated plasma angiotensin I level and plasma renin activity. These results clarified the inhibitory effect of MK-0521 on ACE. In contrast, in the chronic stage of hypertension, MK-0521 showed no depression of plasma angiotensin II. There were no significant changes in daily urinary volume, and renal clearances of sodium, potassium and creatinine. These results suggest that the major mechanism of the antihypertensive effect of MK-0521 in 2-kidney Goldblatt hypertensive dogs is an inhibition of the ACE. In addition, the different effects in the acute and chronic hypertensive dogs suggest that some differences exist in the mechanisms of maintaining blood pressure between the two stages of 2-kidney Goldblatt hypertensive dogs.
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PMID:[Antihypertensive effect of repeated oral administration of MK-0521 in 2-kidney Goldblatt hypertensive dogs]. 254 80


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