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:3.4.23.15 (renin)
35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Standard laboratory rats were maintained on a daily regimen involving deprivation of fluids for 22 h followed by a 2-h opportunity to drink water and a sweetened alcoholic beverage. Angiotensin II, in doses ranging from 0.1 to 1.25 mg/kg, dose relatedly decreased rats' mean intake of ethanol. All doses increased rats' mean intake of water. Angiotensin II, 0.25 mg/kg, reliably reduced intake of ethanol when it was presented alone during the 1st h of the daily 2-h drinking session, and reliably increased intake of water when it was subsequently presented alone during the 2nd h. Thus the reduction in intake of ethanol seen when the alcoholic beverage is presented concurrently with water is probably not merely due to the increase in intake of water. Lisinopril, an angiotensin converting enzyme inhibitor, in doses of 0.3, 1.0, and 3.0 mg/kg, dose relatedly decreased intake of ethanol, but only after several days of injections. Concurrent intake of water was increased dose relatedly. When injections of lisinopril ceased, intakes of both ethanol and water took several days to return to control levels. Pretreatment with lisinopril, 3.0 mg/kg, for 8 days, had no effect on subsequent intakes of either water or ethanol. Lisinopril, 3.0 mg/kg, had no effect on rats' intake of a sweet solution without ethanol. These results confirm previous work and extend the data base supporting the idea that the renin-angiotensin system plays a role in modulating intake of ethanol.
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PMID:Manipulations of the renin-angiotensin system and intake of a sweetened alcoholic beverage among rats. 131 Feb 48

Lisinopril is an orally active, nonsulfhydryl angiotensin-converting-enzyme (ACE) inhibitor that is not metabolized or bound to protein. Peak serum concentrations occur 6-8 h after oral dosing. Lisinopril bioavailability (approximately 25%) is not significantly affected by food, age, or coadministration of hydrochlorothiazide (HCTZ), propranolol, digoxin, and glibenclamide. Lisinopril is excreted unchanged in the urine. Steady state is achieved in 2-3 days with little accumulation. Significant accumulation occurs in patients with severe renal impairment (creatinine clearance less than or equal to 30 ml/min). Lisinopril inhibits ACE activity, thereby reducing plasma angiotensin II and aldosterone and increasing plasma renin activity. Lisinopril produces a smooth, gradual blood pressure (BP) reduction in hypertensive patients without affecting heart rate or cardiovascular reflexes. The antihypertensive effect begins within 2 h, peaks around 6 h, and lasts for at least 24 h. Lisinopril produces greater systolic and diastolic BP reductions than HCTZ. Lisinopril is similar to atenolol and metoprolol in reducing diastolic BP, but superior in systolic BP reduction. Lisinopril and nifedipine produce comparable reductions in systolic and diastolic BP. When lisinopril is given once daily as monotherapy, the range of BP reductions is 11-15% in systolic and 13-17% in diastolic. HCTZ addition enhances its antihypertensive effect. Lisinopril does not produce hypokalemia, hyperglycemia, hyperuricemia, or hypercholesterolemia. Lisinopril has natriuretic properties; renal blood flow remains stable or increases. Lisinopril increases cardiac output, and decreases pulmonary capillary wedge pressure and mean arterial pressure in patients with congestive heart failure refractory to conventional treatment with digitalis and diuretics. Human experience to date (2,800 patients/subjects) indicates that lisinopril is well tolerated and has a good safety profile.
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PMID:The clinical pharmacology of lisinopril. 244 49

The acute hemodynamic, hormonal, and pharmacokinetic aspects of treatment with the angiotensin-converting enzyme (ACE) inhibitor lisinopril were assessed in two studies in 24 patients with chronic stable congestive heart failure (CHF). Lisinopril, the lysine analogue of enalaprilat, is biologically active following absorption and is cleared via the urine without any known metabolic transformation. In the hemodynamic study, single doses of lisinopril (1.25-10.0 mg) were administered on days 1 and 3, each followed by 48 h of intensive hemodynamic observation in 12 patients. Arterial and mixed venous blood from the right atrium were sampled frequently and assayed for angiotensin I, angiotensin II, ACE activity, plasma renin activity, renin substrate, plasma aldosterone, and serum drug concentration. Across all doses, reductions in mean arterial pressure (-17.2%), mean pulmonary capillary wedge pressure (-28.0%), and systemic vascular resistance (-25.6%) were observed compared to baseline values. No significant changes in heart rate or cardiac index were observed. The analysis of the hormonal parameters indicate potent inhibition of the renin-angiotensin-aldosterone system for a period exceeding 24 h. In the pharmacokinetic study, 12 hospitalized patients with chronic CHF received lisinopril both orally and intravenously, with each dose followed by a 72-h arterial blood and urine sampling schedule. Arterial blood pressure was monitored continuously for 6 h following each dosage using an intraarterial cannula. Mean urinary recovery of lisinopril was found to be 15% following oral administration and 88% following intravenous administration. Maximal serum drug concentration occurred at 6 h after oral drug.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hemodynamic, hormonal, and pharmacokinetic aspects of treatment with lisinopril in congestive heart failure. 244 58

After a 2-4 week no-treatment period, 24 patients (12 young, age 29-45 yr.; 12 elderly, age 65-81 yr.; 20 black, 4 white) with an untreated sitting diastolic blood pressure between 91-120 mm Hg received the nonsulfhydryl angiotensin converting enzyme inhibitor, lisinopril for three weeks in a singleblind, parallel group comparison. Patients who did not achieve goal blood pressure with the initial low-dose (10 mg/day) were treated with a high-dose regimen (40 mg/day) for three weeks. In those who remained incompletely responsive, hydrochlorothiazide 25 mg/day was added for four weeks in an attempt to normalize blood pressure (less than or equal to 90 mm Hg). Low-dose lisinopril monotherapy produced comparable reductions in the mean systolic and diastolic blood pressures (approximately -15/-8 mm Hg in both younger and older patients). Increasing the dose produced a slightly greater fall in mean blood pressures which normalized the blood pressure in five of six elderly patients unresponsive to the lower dose; addition of hydrochlorothiazide normalized three of the five remaining subjects from both groups who were unresponsive to high dose lisinopril. Lisinopril administration resulted in a rise in plasma renin activity and a fall in plasma aldosterone concentrations which were similar in both groups and which returned over time toward the baseline. The drug was well tolerated, producing one episode of symptomatic hypotension following the addition of hydrochlorothiazide to lisinopril monotherapy. Lisinopril alone or in combination with hydrochlorothiazide produces favorable antihypertensive effects in both younger and older predominantly black, low-renin patients with essential hypertension.
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PMID:The antihypertensive response to lisinopril: the effect of age in a predominantly black population. 254 Feb 24

We studied the effects of lisinopril on mean arterial blood pressure (MAP), plasma renin activity (PRA), and renal hemodynamics in nine patients with chronic renal disease and hypertension, before, and after three months of therapy. Lisinopril normalized blood pressure in five of nine patients (responders) and did not in the remaining four (nonresponders). PRA rose after lisinopril (4.8 +/- 2.6 ng/mL/h to 25 +/- 15 ng/mL/h, P less than 0.05) in responders, but not in nonresponders (2.0 +/- 1.4 ng/mL/h to 3.4 +/- 2.9 ng/mL/h). Glomerular filtration rate remained stable in both groups (responders: 43 +/- 11 mL/min to 43 +/- 22 mL/min; nonresponders: 39 +/- 25 mL/min to 32 +/- 21 mL/min). In the responders renal hemodynamics remained stable after lisinopril (renal plasma flow: 223 +/- 80 mL/min to 216 +/- 91 mL/min; filtration fraction: .20 +/- .04 to .20 +/- .05; renal vascular resistance: 386 +/- 179 to 326 +/- 209 units). In the nonresponders, renal plasma flow decreased (228 +/- 141 mL/min to 162 +/- 117 mL/min, P less than 0.005), filtration fraction increased (.19 +/- .08 to .24 +/- .12, P less than 0.05), and renal vascular resistance increased (695 +/- 747 to 1265 +/- 1574 units, P less than 0.05) after chronic lisinopril therapy. We conclude (1) there is a heterogeneous response to lisinopril in patients with chronic renal disease and hypertension, (2) lisinopril monotherapy may result in effective blood pressure control without renal hemodynamic compromise, and (3) an increase in PRA following converting enzyme inhibition may identify those in whom the circulating renin angiotensin system is participating in systemic hypertension and intrarenal hemodynamic changes.
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PMID:Hemodynamic responses to converting enzyme inhibition in patients with renal disease. 255 29

Established essential hypertension is characterised haemodynamically by a normal cardiac output and elevated total peripheral resistance. As hypertensive cardiovascular disease progresses, and the patient grows older, cardiac output falls and total peripheral resistance is further elevated. The activity of the renin-angiotensin-aldosterone (RAA) system declines throughout life and reaches its lowest levels in the elderly, unless there is congestive heart failure. In long-standing hypertension, target organ disease such as left ventricular hypertrophy, nephrosclerosis and cerebrovascular damage is commonly observed. Rational antihypertensive therapy should therefore aim to lower total peripheral resistance, spare cardiac output, and maintain or improve blood flow to target organs. ACE inhibitors lower arterial pressure by decreasing total peripheral resistance, they maintain or improve cardiac contractility, promote regression of left ventricular hypertrophy, and increase renal blood flow. Lisinopril is a novel ACE inhibitor that does not contain a sulphydryl group. It is not a prodrug and thus does not require bioactivation by the liver. Lisinopril has a long duration of action, allowing it to be used as a single daily dose in the treatment of hypertension. Preliminary studies from our laboratory indicate that lisinopril reduces cardiac output and preload to the left ventricle. Lisinopril also reduces left ventricular hypertrophy and lowers renal vascular resistance, thereby increasing renal blood flow. In patients with mild to moderate hypertension, lisinopril is more effective than hydrochlorothiazide in reducing both systolic and diastolic blood pressure, and is at least as effective as atenolol or metoprolol in reducing diastolic blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lisinopril in the treatment of hypertension. 255 Jun 40

Nineteen essential hypertensive patients were entered into a protocol to assess the BP, humoral and renal effects of the angiotensin converting enzyme inhibitor, lisinopril (MK 521, 20 to 80 mg once daily), administered for 52 weeks. Specifically monitored prior to, and following 12 and 52 weeks of lisinopril monotherapy were plasma renin activity and plasma aldosterone, the clearances of creatinine, inulin and para-aminohippurate, and the 24-hour urinary excretion of protein. BP was well controlled. Plasma renin activity was stimulated, and plasma aldosterone was suppressed throughout the entire protocol. In contrast to the reported short-term and long-term renal effects of enalapril, lisinopril (a lysine analog of enalapril) had no short-term effect on renal function: glomerular filtration rate, effective renal plasma flow, filtration fraction (FF), renal vascular resistance (RVR), and protein excretion were all unchanged. However, following long-term therapy, both FF and RVR were decreased. Lisinopril appears to convey no specific renal pharmacological benefit.
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PMID:Effect of lisinopril monotherapy on renal hemodynamics. 283 83

The interaction of salt with hypertension-induced left ventricular hypertrophy and its reversal by inhibition of angiotensin converting enzyme were studied in salt sensitive and salt resistant Dahl rats. Eight-week-old rats were fed either a low or high salt diet for three weeks. The colonies were then further divided and either treated with lisinopril or given no treatment for 11 weeks. Untreated salt sensitive rats had higher blood pressures than salt resistant animals. Left ventricular weight and wall thickness in both untreated salt sensitive groups was higher than in the resistant groups. Therapy lowered blood pressures in all groups but those of the high salt group remained higher than the low salt group. Reduction of left ventricular weight and wall thickness took place in either strain only when salt intake was low. Right ventricular and atrial weights were largely unaffected either by salt intake or drug therapy. Plasma renin activity increased and aldosterone levels decreased with lisinopril therapy in all groups except the salt sensitive, high salt group where both remained unchanged at low levels. Lisinopril was effective in reducing blood pressure and left ventricular hypertrophy, but both effects were severely impaired by high salt intake. The major determinant of left ventricular hypertrophy appeared to be afterload, as shown by a good correlation between left ventricular mass and systolic blood pressure, but there was some indication of a possible independent hypertrophic action of salt.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Correlation of left ventricular hypertrophy and its regression by lisinopril with salt-induced hypertension. 284 21

Angiotensin-converting enzyme inhibitor therapy has been thought to be more effective in hypertensive patients with normal or elevated levels of renin in the plasma. However, several studies have challenged this concept by demonstrating the efficacy of angiotensin-converting enzyme inhibitors (captopril and enalapril) in older patients, among whom a low level of renin activity in the plasma is common, and in other patients with low-renin essential hypertension. Lisinopril, a new long-acting angiotensin-converting enzyme inhibitor, also has been shown to be an effective antihypertensive agent in older patients. This report examines data from 97 older and 710 younger hypertensive patients enrolled in four multicenter trials of eight to 12 weeks' duration. In these trials, the dose of lisinopril was titrated until a diastolic pressure of less than 90 mm Hg was reached, or to a maximal dose of 80 mg per day. In general, the antihypertensive effect achieved in older patients with lisinopril was equal to or greater than that achieved in younger patients. The drug was generally well tolerated. Lisinopril can be expected to be used frequently in older patients.
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PMID:Efficacy and safety of lisinopril in older patients with essential hypertension. 284 85

The comparative effects of lisinopril, a third generation angiotensin converting enzyme (ACE) inhibitor, on components of the renin-angiotensin system were assessed in normal and in an animal model of diabetes-related hypertension, the streptozotocin-diabetic rat. Two weeks after injection of streptozotocin the mean systolic blood pressure of diabetic rats was elevated 11% above that of normal rats. This effect was prevented by daily injection of insulin. The mean serum ACE activity was elevated 71% above that of normal rats. Lisinopril reduced systolic blood pressure and inhibited serum ACE activity in both normal and diabetic rats in a dose-response fashion. In normal rats maximum inhibition of blood pressure occurred at a mean dose of 1.0 mg/kg and in the diabetic rat at a mean dose of 5.0 mg/kg. At a mean dose of 5 mg/kg, ACE was inhibited by 100 and 92% in normal and diabetic rats, respectively. Plasma renin activity (PRA) increased sharply in both groups of rats treated with the lower doses of lisinopril, only to decrease at the 5 mg/kg level. At 20 mg/kg, PRA continued to decline in normal animals, but not in diabetic rats. Formation of angiotensin II (Ang II) in both normal and diabetic rats was maximally inhibited at doses of 1.0 and 0.1 mg/kg of lisinopril, respectively without a significantly greater effect at the higher doses of the drug. In separate experiments the effects of chronic treatment with lisinopril at two dosage levels on various physiological parameters of streptozotocin-diabetic rats were compared with the effects of another hypotensive agent, hydralazine, an arteriolar vasodilator.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of the angiotensin converting enzyme inhibitor, lisinopril, on normal and diabetic rats. 284 85


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