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

Cicletanine (CIC), a furopyridine derivative, lowers blood pressure in hypertensive animals and humans. We have previously identified an NaCl-sensitive substrain of spontaneously hypertensive rat (SHR-S) that displays enhanced sensitivity to the depressor effects of exogenous atrial natriuretic peptide (ANP) when fed a high NaCl diet. The current study tested the hypotheses that CIC has an exaggerated antihypertensive effect in NaCl-supplemented SHR-S and that this effect might be ANP dependent. CIC (40 mg/kg/day) or vehicle was administered by gavage in a single daily dose for three weeks beginning immediately prior to initiation of 1% or 8% NaCl diets in seven-week-old male SHR-S. CIC significantly decreased mean arterial pressure (MAP) and the ratio of left ventricular and septum weight to body weight (LV + S/BW) in both 8% NaCl- and 1% NaCl-fed SHR-S. The depressor effect of CIC was greater in the 8% NaCl group (-26 mmHg) than in the 1% NaCl group (-13 mmHg). CIC was associated with significant reduction in RAP in the 8% NaCl group but not in the 1% NaCl group. Neither CIC treatment nor 8% NaCl significantly altered plasma ANP or cyclic guanosine monophosphate (GMP) levels in plasma, aorta, or kidney. CIC was associated with significant decreases in plasma norepinephrine (NE) levels in the 1% NaCl group but not in the 8% NaCl group. The data demonstrate that the antihypertensive effect of CIC is exaggerated in NaCl-sensitive hypertension. The antihypertensive effect of CIC appears not to be related to ANP or cyclic GMP but may be related to a combination of a sympatholytic and natriuretic/diuretic effects in SHR-S.
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PMID:Antihypertensive effect of cicletanine is exaggerated in NaCl-sensitive hypertension. 164 1

We designed experiments to reveal the antihypertensive properties of cicletanine, a novel antihypertensive drug, in Dahl salt-sensitive (Dahl-S) rats. Cicletanine (39 mg/kg body weight per day for 6 weeks) ameliorated the development of hypertension in Dahl-S rats fed a high-salt (4% NaCl) diet. This blood pressure reduction was associated with a decrease in heart weight and vascular wall thickness. Moreover, urinary prostacyclin (PGl2) excretion was increased with cicletanine treatment, being inversely related to systolic blood pressure. Proteinuria and urinary excretion of n-acetyl-beta-D-glucosaminidase were decreased and glomerular filtration rate was increased with this treatment. Morphological investigation revealed an improvement in glomerulosclerosis, renal tubular damage and intrarenal arterial injury in the salt-induced hypertensive rats. In contrast, trichloromethiazide, which decreased blood pressure to the same extent as cicletanine, lowered urinary PGl2 excretion and generally did not ameliorate the deteriorated renal functions and morphological abnormalities. Thus, these data indicate that cicletanine ameliorates the development of hypertension in Dahl-S rats and protects the cardiovascular and renal systems against the injuries seen in the hypertension. The enhanced vasodepressor PGl2 synthesis probably participates, to some extent, in these beneficial properties of long-term cicletanine treatment.
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PMID:Antihypertensive effects of cicletanine and renal protection in Dahl salt-sensitive rats. 165 82

We designed experiments to investigate the effects of cicletanine, a novel antihypertensive drug, on medial hypertrophy in Dahl rats susceptible to salt-induced hypertension (Dahl S rats). Cicletanine treatment (500 mg of cicletanine/kg of chow) for 6 weeks lowered blood pressure by 19% in Dahl S rats challenged with a high-salt (4%) diet. The blood pressure reduction was associated with a significant decrease in weight of the aortic vessels. Morphological examination revealed that this treatment decreased medial hypertrophy and expansion of intimal tissue, in concert with resolution of the periarteritis in the intrarenal arteries. In fact, the content of actin in the aortic wall, analyzed by SDS-PAGE, was decreased significantly with this treatment and myosin content was reduced to the same extent as well. Moreover, cicletanine per se lowered protein synthesis in randomly cycling cultured vascular smooth muscle cells (VSMCs) from Sprague-Dawley rats. Actin formation by VSMCs was decreased with cicletanine. Thus, these data indicate that chronic cicletanine treatment produces regression of the medial hypertrophy in Dahl S rats. Direct inhibitory effects on cytoskeleton protein synthesis, as well as its antihypertensive action, are partly responsible for this regression in vivo.
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PMID:Evidence for medial-mass regression in the vascular wall of Dahl hypertensive rats by cicletanine treatment. 171 85

1. The vascular effects of cicletanine have been studied in vitro on ring preparations of inferior epigastric arteries from normotensive human females and human females with pregnancy-induced hypertension (preeclampsia). 2. Cicletanine (10(-7)-10(-3) M) elicited concentration-dependent relaxation of vessels precontracted with 10(-7) M noradrenaline (NA) or 60 mM K+ but was more potent in the former. Relaxation was significantly greater in rings from preeclamptic patients and was uninfluenced by endothelium removal. 3. The intracellular Ca-dependent contractile responses to 10(-5) M NA in Ca-free medium as well as the subsequent extracellular Ca-dependent contractions (on restoration of external Ca) were significantly attenuated dose-dependently by cicletanine (10(-5) M, 3 x 10(-4) M) in arterial rings from both normotensive and preeclamptic patients. Cicletanine also relaxed rings precontracted by 25 mM K+ but was ineffective against 80 mM K(+)-induced contractions. 4. The inhibition of intracellular Ca-dependent contractions was significantly greater in rings from preeclamptic than from normotensive patients whereas extracellular Ca-dependent contractions were comparably inhibited in both groups. Nifedipine, on the other hand, had little effect on the intracellular Ca-dependent contractions but significantly depressed extracellular Ca-dependent contractions. 5. Cicletanine-induced relaxation was uninfluenced by pretreatment with propranolol, ouabain, tetraethylammonium, procaine, indomethacin, cimetidine or tetrodotoxin but was antagonized by glibenclamide. 6. The results show that cicletanine inhibits contractile responses of human isolated inferior epigastric arteries by a mechanism unrelated to endothelial factors but associated with inhibition of calcium metabolism. An action of cicletanine on glibenclamide-sensitive K+ channels is also suggested. Cicletanine-induced inhibition was significantly greater in arteries from preclamptic patients.
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PMID:In vitro vascular effects of cicletanine in pregnancy-induced hypertension. 191 87

Cicletanine, when given p.o. either acutely or subchronically, was found to produce a clear-cut antihypertensive effect in the deoxycorticosterone salt experimental rat model. This compound was able to reverse high blood pressure, even at doses deprived of diuretic effect. Subchronic treatment (30 mg/kg, p.o.; 14 days) with cicletanine reduced the enhanced contractile response to noradrenaline in deoxycorticosterone salt rat aortic strips and reversed the cardiac hypertrophy in these animals. The antihypertensive effect after long-term treatment with cicletanine in deoxycorticosterone salt rats appears to be related to an antagonism of the elevated sympathetic drive to the vascular smooth muscle.
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PMID:The antihypertensive agent cicletanine reverses vascular hyperreactivity to noradrenaline and cardiac hypertrophy in DOCA-salt rats. 215 59

Cicletanine is a new antihypertensive agent. In view of its various pharmacological properties and of the different factors involved in sudden death, cicletanine was tested on an ischaemia-reperfusion model in anaesthesized dogs. In these experiments myocardial reperfusion induced ventricular fibrillation in 87 p. 100 of the cases, where as only 20% of those animals who received cicletanine 20 mg/kg intravenously 15 minutes before the 30 minute coronary occlusion developed ventricular disorders (p less than 0.001 vs controls). Moreover, cicletanine showed good antiarrhythmic activity during occlusion (total number of arrhythmias: 73.0 +/- 23.15 in treated animals, as against 293.4 +/- 40.03 in controls; p less than 0.05). Thus, antihypertensive treatment with cicletanine may prevent some of the cardiovascular risks associated with arterial hypertension.
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PMID:[Effect of cicletanine on a sudden death model in dogs]. 251 57

Cicletanine is a new antihypertensive agent known for being able to stimulate prostaglandin synthesis in vivo and in endothelial cell cultures. The drug was administered to spontaneously hypertensive rats (SHP-SP) whose hypertension was enhanced by a high sodium content diet. Cicletanine prolonged the animals' survival and reduced the severity of histological renal lesions. PGE2, PGI2 and thromboxane A2 assays performed in renal tissues showed a highly significant increase of PGE2 (a prostaglandin involved in the regulation of renin synthesis) in SHR-SP rats treated with oral cicletanine in daily doses of 30 mg/kg. A less significant increase of PGI2 was found in renal tissues, whereas only slight variations in thromboxane concentrations were observed. The favourable therapeutic effect obtained with cicletanine in the treatment of hypertension may be due, at least in part, to the stimulation of PGE2 and PGI2 production in renal tissue.
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PMID:[Effects of treatment with cicletanine on kidney PGE2 and PGI1 in spontaneously hypertensive rats]. 251 66

The purpose of this study was to evaluate the level of renal synthesis of vasodilator and natriuretic prostaglandins I2 and E2 in patients with essential hypertension and to test the effect of cicletanine, a new antihypertensive drug, on the renal synthesis of these prostanoids in hypertensive patients. The first part of the study was carried out in 12 healthy normotensive subjects and in 25 patients of both sexes with essential hypertension. The effect of cicletanine administered in dose of 150 mg was assessed in 10 healthy volunteers and 12 hypertensive patients. The urinary levels of prostaglandins 6-keto-PGF1 alpha (a metabolite of prostacyclin PGI2) and PGE2 were measured (HPLC) by radioimmunoassay after extraction and chromatographic separation. In normal subjects the urinary excretion rate of 6-keto-PGF1 alpha was 134 +/- 26 pg/min and that of PGE2 was 180 +/- 25 pg/min. The corresponding values were significantly lower in hypertensive patients. This defect of PGI2 and PGE2 renal synthesis was found in 64 p. 100 and 72 p. 100 respectively of patients with hypertension. Cicletanine increased the urinary excretion of 6-keto-PGF1 alpha by 45 p. 100 and that of PGE2 by 59 p. 100 in hypertensive patients. It also brought to normal limits the secretion of these prostanoids in these subjects. At the dose of 150 mg the drug stimulated natriuresis significantly and increased glomerular filtration in patients with essential hypertension. This renal effect of cicletanine was acutely reduced by the presence of indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Reduction of kidney prostaglandin synthesis in patients with essential hypertension. Stimulating effect of cicletanine]. 251 74

Moderate arterial hypertension of the elderly has to be treated but the efficacy has to be progressive. Cicletanine has a pharmacokinetic profile well fitted to the therapy of this age group. The mechanism of action is characterized by synthesis of prostacyclin. A double blind prospective randomized study was conducted at two institutions on 132 patients aged more than 60, with diastolic arterial pressure over 95 mmHg and systolic over 160 mmHg. 62.9% of them were aged more than 75. The analysis of those two studies shows that the three groups with cicletanine (respectively 50, 100 and 150 mg per day) had a significant decrease of both pressures versus placebo. In the 50 mg group, 40% of arterial pressures were normalized after 3 months of treatment. There were no difference between 50 and 100 mg. There were no adverse drug reaction like falling down, day or night, or orthostatic hypotension. The biological tolerance, more particularly renal, was excellent with this dose of 50 mg a day. Cicletanine at the dose of 50 mg/day is a recommended treatment in arterial hypertension of the elderly.
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PMID:[Efficacy and tolerability of cycletanine in aged patients with hypertension]. 275 15

Cicletanine, a new furopyridine derivative synthetized by the Institut Henri Beaufour (France) was found to work as an efficient antihypertensive agent in DOCA-salt rats. This compound also inhibited the development of cardiac hypertrophy characteristic of this sort of hypertension. The mechanism of antihypertensive action at nondiuretic doses of cicletanine remains to be studied.
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PMID:The effect of acute and subchronic treatment with cicletanine on DOCA-salt hypertension in the rat. 280 77


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