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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitrendipine and cilazapril are two new antihypertensive drugs with different mechanisms of action. Nitrendipine is a calcium antagonist of the dihydropyridine class which decreases directly the smooth muscle tone. Cilazapril is a new long-lasting inhibitor of angiotensin-converting enzyme which suppresses the peripheral vasoconstrictor effect of angiotensin I by inhibiting its transformation in angiotensin II. The goal of the present study was to assess the effects on hemodynamics and regional blood flows (measured with radioactive microspheres) of cilazapril and nitrendipine given alone or in combination. Cilazapril (3 mg/kg) and nitrendipine (0.3 mg/kg) were given intravenously to conscious spontaneously hypertensive rats first alone, then in combination. Both cilazapril and nitrendipine decreased mean arterial pressure to the same extent. Cilazapril increased regional blood flow only in the kidney without changing total cardiac output. In contrast, nitrendipine increased regional blood flow in nearly every organ and markedly enhanced total cardiac output. Cilazapril redistributed the cardiac output distribution toward the kidney, and nitrendipine did not change the cardiac output distribution. The combination of both nitrendipine and cilazapril produced a stronger antihypertensive effect than each drug alone. The peripheral vasodilatation with the combination was not as marked as with nitrendipine alone but was associated with the same redistribution of the cardiac output toward the kidney as with cilazapril. We conclude that after acute intravenous administration the combination of cilazapril and nitrendipine produced hemodynamic effects which cannot be induced by each drug used alone. Such a therapeutic profile may be useful in patients with high blood pressure or heart failure.
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PMID:Effects of nitrendipine and cilazapril alone or in combination on hemodynamics and regional blood flows in conscious spontaneously hypertensive rats. 246 61

Left ventricular hypertrophy due to hypertension is associated with a decrease of coronary vascular reserve. We have previously shown that chronic angiotensin converting enzyme (ACE) inhibition prevents cardiac hypertrophy and improves coronary vascular reserve when the treatment is started before appearance of hypertension in spontaneously hypertensive rats (SHR). However, the effects of starting chronic ACE inhibition when hypertension was already developed is not known. The goal of the present study was to assess the effects of chronic ACE inhibition on coronary vascular reserve and on the morphology of the coronary microvasculature when treatment was started after hypertension had developed. For this purpose, one group of SHR was treated from 3-8 months of age with cilazapril, a new ACE inhibitor, and compared with a group treated by placebo. At the end of treatment, cardiac hypertrophy, coronary vascular reserve, density and cross-sectional surface area of the myocardial capillaries (normalized for the myocardial mass) and wall/lumen ratio of the coronary arterioles were determined. Chronic ACE inhibition with cilazapril reduced cardiac hypertrophy and improved by more than 50% coronary vascular reserve in the left and right ventricles. In the left ventricle, the improvement was more pronounced in the subendocardium than in the subepicardium. Cilazapril increased the density and the cross-sectional surface area of the myocardial capillaries and decreased the wall/lumen ratio of the arterioles of the left ventricle. We conclude that chronic ACE inhibition can improve coronary vascular reserve, increase capillary density and capillary cross-sectional surface area and decrease the thickness of the media of coronary arterioles in SHR even when treatment is started after development of hypertension.
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PMID:Effects of chronic ACE inhibition on cardiac hypertrophy and coronary vascular reserve in spontaneously hypertensive rats with developed hypertension. 252 24

1. Six healthy subjects received cilazapril (2.5 mg once daily), propranolol (120 mg once daily), the combination of both and placebo for a period of 1 week each (wash-out phase 1 week). 2. Propranolol and cilazapril reduced systolic and diastolic blood pressure (BP) by 7 mm Hg at peak when compared with placebo. However after the combination, this reduction was more than doubled (18 mm Hg) and lasted longer. 3. There was a trend to lower and later peak concentrations for both drugs after administration of the combination. No clinically relevant pharmacokinetic interactions between cilazapril and propranolol were found. 4. The effects on blood pressure were confirmed in hypertensive patients (BP diastolic greater than 95 mm Hg). Thirteen patients were randomly allocated cilazapril (2.5 mg day-1) or propranolol (120 mg day-1] as part of a cross-over design. This was then followed by the combination. All treatment periods were of 3 weeks duration and all measurements were done 2 h after drug administration. 5. Cilazapril lowered the median sitting diastolic BP by 8 mm Hg, and propranolol by 9 mm Hg, whereas the combination reduced the diastolic BP by 19 mm Hg. 6. The results of these studies, attempting to elucidate drug-drug interactions, showed that combined use of propranolol and cilazapril resulted in a more pronounced and longer lasting blood pressure reduction, in healthy subjects and in patients with hypertension.
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PMID:Pharmacokinetic and pharmacodynamic interactions between the ACE inhibitor cilazapril and beta-adrenoceptor antagonist propranolol in healthy subjects and in hypertensive patients. 252 45

Chronic hypertension is associated with a lower cerebral vascular reserve due to thickening of the media of cerebral vessels. The goal of the present study was to determine if long-term inhibition of angiotensin converting enzyme with cilazapril, a new long-acting angiotensin converting enzyme inhibitor, could improve cerebral vascular reserve. For this purpose, two groups of 12 spontaneously hypertensive rats were compared. One group was treated with 10 mg/kg/day cilazapril from 14 weeks to 33 weeks of age and was compared with a group treated with placebo. A third group of 12 Wistar-Kyoto rats treated with placebo was used as reference. At the end of the treatment period, cerebral vascular reserve was evaluated by measuring cerebral blood flow (radioactive microspheres) at rest and during maximal vasodilation induced by seizures provoked by bicuculline. Then, the rats were perfusion-fixed, and morphometry of the cerebral vasculature was performed. Cerebral vascular reserve was severely impaired in the spontaneously hypertensive rats since their maximal cerebral blood flow was decreased by 52% compared with the Wistar-Kyoto rats. Cilazapril normalized cerebral blood flow reserve. This normalization was associated with a decreased thickness of the medial layer in the carotid artery, the middle cerebral artery, and in the pial arteries larger than 100 microns. Further studies are required to determine whether this decreased medial thickness is due to the normalization of blood pressure induced by cilazapril or to the reduction of trophic factors such as angiotensin II.
Hypertension 1989 Dec
PMID:Effects of cilazapril on the cerebral circulation in spontaneously hypertensive rats. 253 Nov 20

The effect of cilazapril, a new inhibitor of angiotensin-converting enzyme, in a dosage of 2.5 or 5 mg once daily, was compared with that of hydrochlorothiazide 25 or 50 mg in 169 patients with mild to moderate hypertension. Blood pressure at entry was 158/103 mm Hg (cilazapril) and 160/103 mm Hg (hydrochlorothiazide). Cilazapril 2.5 mg caused a decrease in blood pressure of 14.7 +/- 2.3/12.6 +/- 1.2 mm Hg compared with a decrease of 12.6 +/- 2.2/10.2 +/- 1.2 mm Hg with hydrochlorothiazide 25 mg. Those patients who required an increase of dosage to the higher level then showed decreases of 15.0 +/- 2.1/14.3 +/- 1.2 (cilazapril) and 19.7 +/- 1.9/13.3 +/- 1.2 hydrochlorothiazide. All decreases in blood pressure were statistically significant but were not statistically different from each other. Fifty-one percent of patients reached a sitting diastolic blood pressure of 90 mm Hg or less receiving 2.5 mg of cilazapril and an additional 28 percent of patients reached this goal receiving 5 mg. The figures for patients receiving hydrochlorothiazide were comparable: 36 and 35 percent. Twenty-one adverse events remotely, possibly, or probably related to therapy were reported with cilazapril and 32 with hydrochlorothiazide. Three patients withdrew from cilazapril because of mild angioedema, headaches, and chest pain, respectively, and three patients withdrew from hydrochlorothiazide treatment because of fatigue, dizziness, and gastric hemorrhage. Hydrochlorothiazide caused a decrease in potassium levels and an increase in levels of cholesterol, uric acid, urea and - gamma cilazapril had no adverse biochemical effects. Cilazapril lowered blood pressure to the same extent as hydrochlorothiazide. Young patients had better responses to cilazapril than to hydrochlorothiazide. It is concluded that cilazapril is an effective and safe drug for patients with mild to moderate hypertension.
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PMID:Efficacy of cilazapril compared with hydrochlorothiazide in the treatment of mild-to-moderate essential hypertension. Multicentre Study Group. 253 59

Cilazapril is a structurally new angiotensin-converting enzyme inhibitor that lacks a sulfhydryl moiety. Its duration of action is consistent with a once-daily regimen. Cilazapril was studied in multiple-dose trials that included more than 4,500 hypertensive patients worldwide. Approximately 450 patients received cilazapril as monotherapy for more than one year, and another 430 patients were treated with cilazapril in combination with hydrochlorothiazide for more than six months. Cilazapril at doses of 2.5 to 5 mg once daily is clinically and statistically significantly more effective than placebo and as effective after eight weeks of therapy as hydrochlorothiazide, atenolol, propranolol sustained release, captopril, and enalapril at the doses recommended by the manufacturers. The overall incidence of adverse events observed during cilazapril therapy is comparable with that seen with placebo in double-blind studies. Cilazapril 2.5 to 5 mg once daily seems to be better tolerated than hydrochlorothiazide and atenolol. Only five adverse events were reported at an incidence of 1 percent or more in controlled trials; these were headache, dizziness, fatigue, nausea, and chest pain, which all occurred at a frequency similar to that with placebo. Overall, cilazapril is effective and well-tolerated in the treatment of patients with hypertension.
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PMID:Cilazapril: a new non-thiol-containing angiotensin-converting enzyme inhibitor. Worldwide clinical experience in hypertension. 253 61

The effect of cilazapril as monotherapy or in combination with hydrochlorothiazide was assessed in 30 severely hypertensive patients, 23 men and seven women, aged 38 to 68 years, with sitting diastolic blood pressure of more than 115 mmHg. Fifteen patients had left ventricular hypertrophy documented by two-dimensional echo-cardiography. Sitting systolic blood pressure was reduced from 175.8 +/- 2.0 to 143.3 +/- 3.0 mmHg within 25 days of therapy (p less than 0.0001); sitting diastolic blood pressure decreased in the same period from 117.0 +/- 1.0 to 87.8 +/- 2.0 mmHg (p less than 0.0001), whereas heart rate remained unchanged. In 19 patients treated for an average of 48 weeks the therapeutic response was maintained during the long-term period. The mean effective dose was cilazapril 10 mg plus hydrochlorothiazide 12.5 to 25 mg in 90 percent of the patients. Left ventricular mass decreased from 357 +/- 17 to 314 +/- 22 g (nine patients; p less than 0.005) and a correlation (Spearman r = 0.57, p less than 0.01) was found between left ventricular mass and sitting systolic blood pressure before and during treatment. Deceleration half time of peak early diastolic inflow velocity decreased significantly from 128 +/- 9 to 108 +/- 7 msec (p less than 0.05). Glomerular filtration rate and renal blood flow remained within normal limits, whereas renal vascular resistance decreased from 0.16 +/- 0.0 to 0.10 +/- 0.0 resistance units (10 patients; p less than 0.01). Cilazapril in combination with hydrochlorothiazide was effective in the treatment of severe hypertension. Left ventricular hypertrophy regression influenced favorably left ventricular diastolic function in some patients, whereas renal hemodynamics were generally not affected by the therapy.
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PMID:Long-term evaluation of cilazapril in severe hypertension. Assessment of left ventricular and renal function. 253 62

We studied the effect of a single dose of cilazapril, 5.0 mg orally, on systolic and diastolic cardiac function in eight hypertensive patients using a double-blind crossover placebo-controlled design. All patients had concentric left ventricular hypertrophy (measured by echocardiography), unimpaired systolic function (measured by radionuclide ventriculography), and long-standing hypertension treated by a combination of beta-blockers and diuretics. Radionuclide scintigraphy was performed with cilazapril and placebo, given one week apart. A two-week washout period of all cardioactive drugs preceded the study. Within three hours after oral administration of cilazapril, the time to peak filling rate of the left ventricle, expressed as a percentage of diastole, was reduced from 44.5 +/- 13.2 percent to 31.2 +/- 7.2 percent (p less than 0.05). Systolic blood pressure was also significantly reduced by cilazapril. Heart rate was slightly reduced. Left ventricular ejection fraction, peak filling rate, and the absolute time to peak filling rate were not significantly altered. Cilazapril improves a sensitive index of diastolic cardiac function in hypertensive patients.
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PMID:A single dose of cilazapril improves diastolic function in hypertensive patients. 253 63

The effects of cilazapril 2.5 to 5.0 mg every 24 hours orally for one month on blood pressure, renal hemodynamics, and plasma and urinary hormones were investigated in 11 patients with renal disease and hypertension. Six patients had renal failure (pretreatment creatinine clearance of less than 1 ml/second). Both systolic and diastolic blood pressures were significantly decreased in all patients and seven of the 11 required 5.0 mg daily. There was no significant change in the effective renal plasma flow, glomerular filtration rate, or creatinine clearance, although the renal vascular resistance was significantly reduced. Albuminuria was reduced in most patients but the mean change was not significant. The mean plasma potassium concentration rose significantly, but no changes in electrolyte excretion or weight were noted. Mean ambulant plasma renin activity was normal before treatment and rose significantly. Mean ambulant angiotensin II concentrations did not change. Mean ambulant plasma aldosterone concentration and mean urinary aldosterone excretion decreased significantly. Plasma arginine vasopressin and cortisol concentrations did not change. No changes were noted in plasma glucose concentrations, liver function tests, hemoglobin concentrations, or white blood cell or platelet counts. A slight looseness of bowel motions occurred in two patients and was the only side effect recorded. Cilazapril appears to be an effective and safe antihypertensive drug in patients with hypertension and renal disease.
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PMID:Effects of cilazapril on renal function and hormones in hypertensive patients with renal disease. 253 67

Polycystic kidney disease (PKD) is the fourth most common cause of end-stage renal disease and is a common cause of hypertension and associated vascular morbidity. Activity of the renin angiotensin system has been identified as a major component of hypertension and altered fluid and electrolyte physiology in PKD. Activity of this pathway also has been proposed as a potential modulator of structural change in both tubules and the interstitium of the kidney. Cilazapril is a long-acting angiotensin-converting enzyme inhibitor that has been effective in producing vascular remodelling in hypertensive vascular disease. We undertook a study to determine whether therapy with cilazapril would modify the expression of PKD in the Han:SPRD-cy rat, a model of autosomal dominant PKD that closely resembles human disease. Male rats were treated for 4 months, starting at 1 month of age. Control animals were hypertensive by 3 months of age, whereas treated animals were noted to be hypertensive only at the exit assessment (P < 0.001 at 3 months, P = 0.005 at 5 months). At 5 months of age, cilazapril-treated animals had modest but statistically significant reductions in serum creatinine (mean, 1.77 mg/dL v 1.97 mg/dL; P = 0.0006) and morphometrically assessed cyst volume (mean, 0.32 mL v 0.67 mL; P = 0.036). Cilazapril is an effective treatment for hypertension in this model of progressive renal disease and may have benefits beyond the prevention of cardiovascular morbidity.
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PMID:Cilazapril delays progression of hypertension and uremia in rat polycystic kidney disease. 750 69


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