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At least 19 recordsLinked to original sources

PubMed1991

Indapamide potentiates the endothelium-dependent production of cyclic guanosine monophosphate by bradykinin in the canine femoral artery.

Indapamide is a sulfonamide diuretic agent that has antihypertensive properties. In the canine femoral artery, indomethacin reduces the endothelium-dependent relaxation induced by bradykinin, and indapamide restores the response. The aim of this study was to determine whether indapamide affects the release or the effects of endothelium-derived nitric oxide and prostanoids. The effect of indapamide on the production of endothelium-derived nitric oxide and prostacyclin was assessed indirectly by the measurement of the tissue content of cyclic guanosine monophosphate (GMP) and the accumulation of 6-keto-prostaglandin F1 alpha in the incubation medium, respectively. Indapamide did not affect the basal production of either cyclic GMP, cyclic adenosine monophosphate (AMP), or 6-keto-prostaglandin F1 alpha in the presence or absence of indomethacin. Indomethacin decreased the production of cyclic AMP and the release of 6-keto-prostaglandin F1 alpha induced by bradykinin, and this was unaffected by indapamide. Indapamide enhanced the bradykinin-stimulated production of cyclic GMP in the presence of indomethacin and did not affect that evoked by 3 morpholino-sydnonimine, an exogenous donor of nitric oxide. Indomethacin had no significant effect on the production of cyclic GMP stimulated by either bradykinin or 3 morpholino-sydnonimine. These studies demonstrate that the potentiation by indapamide of the relaxation evoked by bradykinin is associated with an enhanced production of cyclic GMP in the presence of indomethacin, which suggests that the production of endothelium-derived nitric oxide is increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Radical scavengers of indapamide in prostacyclin synthesis in rat smooth muscle cell.

Indapamide, a nonthiazide diuretic, exhibits direct vasodilator action as well as natriuretic and diuretic effects. Although calcium antagonist-like activity has been addressed so far, the mechanisms for vasodilator effect are still uncertain. To understand the wide range of indapamide actions, we examined the effects of indapamide on the vascular eicosanoid generation and investigated its mechanisms by using rat vascular smooth muscle cells in culture. Indapamide uniquely increased the prostacyclin generation in the vascular smooth muscle cells in a dose-dependent manner, whereas it did not affect the vasoconstrictor thromboxane A2. Thiazide diuretics lowered the prostacyclin generation, while nonthiazide derivatives did not affect the biosynthesis. Enzymatic analysis revealed that indapamide affected neither [14C]arachidonate liberation nor prostacyclin synthase of the smooth muscle cells. Indapamide eliminated a stable free radical in a cell-free system, lowered the formation of malondialdehyde from lipid peroxides in rat brain homogenate, and reduced lipid peroxidation by the free radical generating system of xanthine-xanthine oxidase. Indeed, the scavenging action of indapamide significantly attenuated the inhibitory activity of 15-hydroperoxy-arachidonate to prostacyclin synthase activity. These results indicate that indapamide diuretic increases prostacyclin generation in the vascular smooth muscle cells possibly through antioxidant effects and that the enhanced prostacyclin generation is partly responsible for its direct vasodilator action.

Animals↗

PubMed1990

Effects of indapamide on endothelium-dependent relaxations in isolated canine femoral arteries.

Indapamide is an effective antihypertensive agent in humans and in experimental hypertensive animals. The aim of the present study was to investigate whether indapamide affects endothelium-dependent and independent relaxations in canine femoral arteries. Rings (with or without endothelium) were contracted with prostaglandin F2 alpha (2 X 10(-6) mol/liter) before the addition, in a cumulative fashion, of relaxing agents. Indapamide (10(-7) to 10(-4) mol/liter) had no direct effect on unstimulated or prostaglandin-stimulated preparations; it did not alter relaxations of preparations with endothelium induced by acetylcholine, bradykinin, adenosine diphosphate or the calcium ionophore A23187. Similarly, it did not affect relaxations induced by sodium nitroprusside, prostacyclin or forskolin in preparations with or without endothelium. Indomethacin shifted the concentration-response curve to bradykinin to the right and did not alter that to the other relaxing drugs. The reduced relaxation to bradykinin was reversed in a concentration-dependent manner by indapamide (10(-7) to 10(-5) mol/liter). In the presence of indomethacin, indapamide shifted the concentration response curve to prostacyclin (in rings with endothelium) and to forskolin (in rings with and without endothelium) to the left. Thus, indapamide does not directly affect endothelium-dependent and independent relaxations. However, when prostanoid production is impaired, indapamide facilitates the release of endothelium-derived relaxing factor(s), and to a lesser extent, the direct action on vascular smooth muscle of prostanoids (prostacyclin) released from the endothelium.

Acetylcholine↗

PubMed1978

[Influence of indapamide on isolated rabbit arteries (author's transl)].

The effect of indapamide, a high ceiling diuretic, antihypertensive drug, was investigated in helically-cut strips of rabbit cerebral, coronary, renal, mesenteric and femoral arteries and aortae. The addition of indapamide in concentrations higher than 3 X 10(-5)M relaxed those arterial strips contracted with prostaglandin F2alpha; the relaxation being greater in cerebral, coronary and renal arteries. Atropine propranolol and aminophylline did not reduce the relaxing effect. Hydrochlorothiazide produced fewer incidences of relaxation. Treatment for 20 min with indapamide (3 X 10(-5) or higher) significantly attenuated the contractile response of mesentric arteries to nicotine and tyramine. Contractile responses to transmural electrical stimulation were not reduced but rather potentiated. The dose-response curve of norepinephrine was not significantly affected by indapamide. The contractile response of nictitating membranes of anesthetized cats to stimulation of preganglionic sympathetic nerves was not influenced by indapamide but was abolished by hexamethonium. It may be concluded that arterial relaxations induced by indapamide are due to a direct action on smooth muscles. Indapamide appears to attenuate the response to nicotine and tyramine by interfering with the mechanism of neuronal amine uptake. However, such does not involve a ganglionic blockade nor a reduction of the release of norepinephrine from adrenergic nerve terminals.

Animals↗

PubMed1979

The effects of long term oral treatment with indapamide on the development of DOCA-salt hypertension in rats: vascular reactivity studies.

The onset of DOCA-salt hypertension in male Sprague-Dawley rats was prevented during 11 weeks of oral treatment with indapamide (0.5, or 10.0 mg/kg) or propranolol (60 mg/kg) administered in the diet. The body weights of the indapamide treated groups were significantly (P < 0.01) greater, at weeks 4, 5, 6, 7 and 11, while the body weights and food intake of the propranolol treated group were significantly (P < 0.05) lower at week 11, than the control group. A significant reduction in heart wet weight (P < 0.001) was measured in the indapamide treated animals only. No significant diuresis nor natriuresis was measured in any group during week 11 of treatment. When all groups were subjected to an increased salt load, four weeks after cessation of drug treatment only the indapamide (10 mg/kg) treated animals failed to show an increased blood pressure. Vascular reactivity studies carried out six weeks after termination of drug treatment, indicated a significant (P < 0.01) reduction in pressor activity elicited by electrical stimulation of the entire sympathetic outflow in indapamide (10 mg/kg) treated pithed rats. No significant difference in the pressor activity elicited by noradrenaline (5 x 10(-8) - 5 x 10(-6) g/kg, i.v.) or tyramine (10(-5) - 5 x 10(-5) g/kg i.v.) was observed in any treatment group. In conclusion, chronic oral treatment with indapamide or propranolol, prevented the onset of DOCA-salt hypertension in rats. A long lasting antihypertensive action of indapamide involving the sympathetic nervous system is also indicated.

Animals↗

PubMed1975

Antihypertensive activity of a new agent, indapamide: a double-blind study.

In a double-blind trail in 22 patients with mild to moderate essential hypertension, indapamide was compared with chlorathiazide and placebo. Dosage levels were set at 5 mg. indapamide and 500 mg. chlorothiazide daily, for 5 days out of 7, and patients were treated alternately, in random sequence, with each drug for a month over a 3-month period. Blood pressure readings and blood chemistry investigations were carried out before and after each treatment period and a careful history was kept of subjective symptoms and patients' tolerance of therapy. The results show that both active treatments produced drops in systolic and diastolic pressures, but were only statisically significant and different from placebo in the case of indapamide. Indapamide also produce much greater subjective improvement (74%) in patients with functional symptoms compared with chlorothiazide (15%). In an overall assessment, indapamide produced an excellent to good response to treatment in 57% of patients. Comparable responses for chlorotiazide and placebo were 25% and 20% respectivlely. Using patients as their own controls to compare the relative effectiveness of the three periods of treatment, indapamide was shown to be more effective than placebo in 65% of cases and more effective han chlorothiazide in 60%. Although patient tolerance of indapamide was slightly better, both drugs were well accepted and no significant changes from baseline levels were noted in any of the laboratory parameters investigated.

Adult↗

PubMed1992

In vitro and ex vivo inhibition of the modification of low-density lipoprotein by indapamide.

The effect of an antihypertensive drug, indapamide, on copper- and endothelial cell-induced peroxidation of human low-density lipoprotein (LDL) was studied and compared with that of drugs previously shown to protect LDL against peroxidation: probucol and vitamin E and other thiazidic and nonthiazidic diuretics (clopamide, hydrochlorothiazide, and furosemide). Incubation with indapamide inhibited in a dose-dependent manner LDL peroxidation induced either by copper ions or by cultured endothelial cells. Both electrophoretic mobility and thiobarbituric acid-reactive substances (TBARS) content of LDL returned to almost normal values in the presence of 1 microM indapamide. This drug was at least 10 times more potent than probucol and vitamin E in inhibiting LDL peroxidation. No inhibitory effect has been observed with clopamide, hydrochlorothiazide, and furosemide in the same experimental conditions. Homozygote Watanabe rabbits were treated orally with indapamide (10 mg/kg/d for 3 days) to evaluate the potential protective effect of the compound on LDL peroxidation in vivo. Purified LDL from placebo and treated rabbits were submitted to peroxidation induced by copper ions, and indapamide was effectively able to protect LDL in these experimental conditions. This effect was especially obvious 6 and 8 h after the start of the incubation when LDL of the placebo-treated animals were modified. The mechanism of action of these drugs was examined in vitro using the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) test and in kinetic studies of arachidonic acid photoperoxidation. Indapamide as well as vitamin E and probucol were effective free radical scavengers, but the other diuretic molecules were not.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1975

A comparative study of the activity of a new agent, indapamide, in essential arterial hypertension.

A single-blind crossover trial was carried out in 38 elderly, hospitalised patients with essential hypertension to compare the hypotensive activity of 5 mg. indapamide daily with 100 mg. chlorthalidone daily. After initial treatment for 10 days with placebo, patients received treatment for 45 days with either indapamide or chlorthalidone and were then crossed over to the alternative drug for a similar period. Potassium supplementation was necessary in 25 of the patients receiving chlorthalidone, but was precribed as a precautionary measure in only 1 patients whilst on indapamide. Results showed that there were significant drops in blood pressure following both active medications, but that the percentage reduction in diastolic pressure was greater after indapamide. Indapamide also proved more effective than chlorthalidone in controlling the patients' subjective and functional symptoms of their hypertension. In an overall assessment of the effectiveness of both drugs, indapamide was judged to be better tolerated as well as more effective than chlorthalidone in 18 of the 38 patients, whilst chlorthalidone was preferred in only 7 instances.

Aged↗

PubMed1978

Fluorometric assay for urinary indapamide.

A sensitive fluorescence method for the determination of indapamide was developed. Reaction of indapamide with sodium hydroxide at 100 degrees yielded a fluorescent product, and addition of formaldehyde to the fluorescent product increased its fluorescence intensity by a factor of three. The assay is sensitive to levels of indapamide of 0.025 microgram/ml in an aqueous solution, and a linear response between 0.025 and 2.0 microgram/ml was observed. The procedure was adapted to the analysis of intact indapamide in urine. Concentrations of indapamide of 0.05 microgram/ml can be detected in dogs given 20 mg of the drug.

Animals↗

PubMed1992

Direct vascular actions of hydrochlorothiazide and indapamide in isolated small vessels.

The mechanism by which thiazides lower peripheral resistance is unresolved. The aim of this study was to investigate the mechanisms of the acute vasodilator action of hydrochlorothiazide and the 'thiazide-like' diuretic indapamide on human, guinea pig and rat small arteries. Vessels were mounted on a myograph and the relaxation profile of both drugs and interactions with K+ channels and the vascular eicosanoid system were studied. Neither drug had any relaxant effect in rat mesenteric vessels and indapamide did not relax human arteries. Hydrochlorothiazide in both human and guinea pig vessels produced significantly more relaxation of noradrenaline than K(+)-constricted vessels (P less than 0.001). Relaxation to hydrochlorothiazide was reduced in the presence of charybdotoxin. Maximal-induced hydrochlorothiazide relaxation was reduced by 64% in human arteries (P less than 0.001) and by 91% in guinea pig vessels (P less than 0.001). Incubation with glibenclamide and indomethacin had no effect on the relaxant activity of hydrochlorothiazide and indapamide. Indapamide-induced relaxation was unaffected in the presence of charybdotoxin. These results show marked differences in the acute vasodilator action of hydrochlorothiazide and indapamide. There appears to be involvement of Ca(2+)-activated K+ channels in the acute vasorelaxant activity of hydrochlorothiazide.

Animals↗

PubMed1975

Antihypertensive action of indapamide. Comparative studies in several experimental models.

1-(4-Chloro-3-sulfamylbenzamido)-2-methyl-indoline (indapamide), after single oral dose administration, showed antihypertensive activity in genetically hypertensive rats, DOCA/saline hypertensive rats, unilaterally-nephrectomised DOCA/saline hypertensive rats and dogs made hypertensive by renal encapsulation. The activity was observed at doses as low as 1-3 mg/kg and lasted at least 48 h. Increasing the dose level considerably prolonged the duration of action but did not substantially enhance the maximum antihypertensive effect. In genetically hypertensive rats indapamide was 30-300 times more potent than furosemide, spironolactone and chlorthalidone. Indapamide had no effect on blood pressure in normotensive rats. In concentrations of 1 X 10(-5) to 1 X 10(-3) g/ml, indapamide antagonised contractions of arterial and venous strips to angiotensin, epinephrine and norepinephrine revealing a direct vascular action. Indapamide has a prolonged saluretic action which in combination with the direct vascular effects may well account for its antihypertensive activity.

Animals↗

PubMed1975

A double-blind study in hypertensive patients of an original new compound, indapamide.

In a double-bind crossover study in 18 patients with essential hypertension, the hypotensive activity of 5 mg. indapamide daily was compared with 40 mg. frusemide daily over a period of 4 months after an initial 15 days on placebo. The overall clinical assessment showed satisfactory blood pressure control in 72% of patients receiving indapamide compared with 57% on frusemide. The weight of patients on active therapy dropped significantly with both products, but to a greater extent with indapamide. Indapamide was well-tolerated by all 18 patients; 3 patients on frusemide developed side-effects. The results of blood chemistry investigations are discussed. Variations in potassium levels during indapamide therapy were modest and did not warrant the use of potassium supplements.

Adult↗

PubMed1979

Action of indapamide on excitation-contraction coupling in vascular smooth muscle.

The effects of indapamide on electrophysiological and mechanical parameters of longitudinal smooth muscle strips isolated from mammalian portal vein were studied by means of a double sucrose gap method associated with a photoelectric device for recording contraction. Indapamide (10(-4) M) reduced both the amplitude of the action potential and the contraction. The calcium inward current decreased and consequently the phasic contraction was also reduced. The potassium outward current was diminished while the tonic contraction was not modified significantly. The depressant nature of the indapamide response could counterbalance the stimulating action of angiotensin II but not that of noradrenaline. The results suggest that indapamide acts primarily on the plasma membrane of vascular smooth muscle by reducing the transmembrane calcium current, although a secondary decrease in the intracellular bound calcium could not be completely excluded.

Action Potentials↗

PubMed1992

Beneficial effect of indapamide in experimental myocardial ischemia.

Indapamide, a nonthiazide chlorosulfamoyl diuretic, which possesses well-known antihypertensive properties, is able to scavenge free radical intermediates involved in lipid peroxidation. In this respect, it has almost the same level of action as alpha-tocopherol. Using an isolated working rat heart preparation, we investigated the effect of indapamide on the myocardial resistance to global total normothermic ischemia followed by reperfusion. The heart, isolated at the end of chronic oral pretreatment (7 day at 3 mg/kg body weight/day), was submitted to ischemia for 15 min and then reperfused. The main results were as follows: in the indapamide-treated group, 1) postischemic recovery of cardiac function was significantly better as compared to the untreated control group; 2) lactate dehydrogenase (LDH) release measured after 15 min of reperfusion was significantly reduced; 3) the myocardial content of organic hydroperoxides (HPO), taken as an index of lipid peroxidation, was significantly lowered, whereas the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) remained unchanged; and 4) electron spin resonance (ESR) analysis of coronary effluents, collected during the first minutes of reperfusion in the presence of the spin-trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO), revealed a significant modification in the treated group. These findings suggest that indapamide treatment is able to afford some protective effect to cardiac tissue during the early stage of postischemic reperfusion, and that this effect might be related to the antioxidant properties of inadapamide.

Animals↗

PubMed1991

Effect of indapamide on the proliferation of Balb/C 3T3 cells induced by platelet-derived growth factor.

The effects of indapamide (a nonthiazide antihypertensive diuretic) on the growth promoting activity of serum, platelet-derived growth factor (PDGF), fibroblast growth factor (FGF) or Ca3(PO4)2 on Balb/C 3T3 cells were studied. Indapamide inhibited the growth promoting activity of serum, but furosemide (a nonthiazide antihypertensive diuretic) had no such inhibitory effect. Indapamide inhibited the growth promoting activity of PDGF, but not that of FGF and Ca3(PO4)2. The present experiments demonstrate that indapamide selectively inhibits the growth promoting activity of PDGF.

3T3 Cells↗

PubMed1992

[The effect of indapamide on plasma prostaglandins in hypertensive patients].

After two weeks' treatment of indapamide (2.5 mg/d) in 30 cases of mild to moderate hypertensive patients, there was a significant decline of systolic and diastolic blood pressure. And 8 weeks after indapamide administration, 2/3 of the total treated patients achieved complete control of hypertension. During the treatment period, there were no changes of serum cholesterol, triglyceride and renal function, except a slight, but still in the normal range, decrease of serum potassium and sodium. Concurrently, plasma vasoconstrictive prostaglandins TXB2 (metabolite of TXA2) and PGF2 alpha reduced significantly (P < 0.01 and P < 0.001 respectively), whereas plasma vasodilative prostaglandins 6-keto-PGF1 alpha (metabolite of PGI2) and PGE2 increased significantly (P < 0.02 and P < 0.05 respectively). The results support the theory that prostaglandins system may play an important role in the hypotensive process of indapamide. The influence of indapamide on prostaglandin system may favour the improvement of platelet function and the maintenance of the homeostasis.

Adult↗

PubMed1991

Regression of left ventricular hypertrophy in hypertension with indapamide.

In hypertensive patients, the development of left ventricular hypertrophy seems to increase the risk of cardiovascular death. Although some antihypertensive agents have been associated with regression in left ventricular hypertrophy, diuretics, the most widely used ones, have not. Indapamide is a new, nonthiazide diuretic and vasodilator. To test its effects on left ventricular hypertrophy, patients with essential hypertension and left ventricular hypertrophy were studied before and at the end of 6 months of therapy with 2.5 mg of indapamide daily. Candidates had to have moderate, uncontrolled essential hypertension with echocardiographically documented left ventricular hypertrophy (left ventricular mass index greater than or equal to 130 gm/m2 for men and greater than or equal to 110 gm/m2 for women). Patients with complicated hypertension or with significant cardiovascular or metabolic diseases were excluded. Patients could remain on antihypertensive drugs other than diuretics, provided doses remained stable for 3 months before entry and there was no know regression of left ventricular hypertrophy. Of 13 patients selected, 2 dropped out. The remaining 11 patients successfully completed 6 months of therapy. The average age was 56 +/- 10 years. Indapamide was associated with a significant reduction of mean systolic blood pressure from 172 to 142 mm Hg (p less than 0.001), diastolic blood pressure from 101 to 83 mm Hg (p less than 0.001), and left ventricular mass index from 146 +/- 22 to 124 +/- 22 gm/m2 (mean +/- SD) (p less than 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMedDate not supplied

Evaluation of indapamide in the treatment of hypertension.

A randomized double-blind, crossover trial was carried out in twenty hypertensive patients to evaluate the hypotensive efficacy and safety of indapamide. Indapamide in doses of 2.5 mg per day in combination with other antihypertensive agents was as effective in reducing the blood pressure in hypertensive patients as one tablet of Moduretic (50 mg hydrochlorothiazide and 5 mg amiloride). Indapamide induced no changes in serum potassium or uric acid levels and there were no major side effects.

Adult↗