sulindac and Hypertension

Angiotensin-converting enzyme inhibitors are widely prescribed for hypertension and heart failure. These drugs are commonly associated with cough, and are less commonly associated with angioedema, which may be potentially life threatening. This review describes data that extend our understanding of the mechanisms of these reactions, and provides guidance about clinical management.. For patients who develop angioedema from angiotensin-converting enzyme inhibitors, recent data are reassuring that the majority of such patients can tolerate angiotensin-II receptor blockers. These data support earlier conclusions that most patients with angiotensin-converting enzyme inhibitor-induced cough can tolerate angiotensin-II receptor blockers. Limited case reports suggest that in acute angioedema induced by angiotensin-converting enzyme inhibitors, patients refractory to standard treatment may benefit from the infusion of fresh frozen plasma.. Although data are incomplete, it appears that angiotensin-converting enzyme inhibitors cause cough and angioedema through a cascade of effects that begins with the accumulation of kinins, and then involves arachidonic acid metabolism and nitric oxide generation. Most patients who develop either cough or angioedema from angiotensin-converting enzyme inhibitors can tolerate angiotensin-II receptor blocking agents.

Topics: Angioedema; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Asthmatic Agents; Anti-Inflammatory Agents, Non-Steroidal; Baclofen; Cough; Cromolyn Sodium; Humans; Hypertension; Muscle Relaxants, Central; Sulindac

To determine the impact of three non-steroidal anti-inflammatory drugs on the efficacy of two anti-hypertensive drugs.. Fifteen women with arthritis and hypertension who were receiving lisinopril and HCT, and administered sequentially in random order ibuprofen, sulindac, and diclofenac for one month each, with an intervening two-week washout period between each treatment period. During the washout period, subjects received paracetamol.. Hypertension Clinic, Medical Centre, Harare, Zimbabwe.. Fifteen female hypertensive women with documented arthritis.. Blood pressure at the end of two weeks of paracetamol was compared with blood pressure after one month of treatment with each of the NSAID.. Mean blood pressure was unchanged before and after all NSAIDs: 108 +/- 7 versus 107 +/- 9 for diclofenac, 108 +/- 9 versus 108 +/- 9 for sulindac, and 108 +/- 8 versus 107 +/- 9 for ibuprofen. The 24 hour urinary sodium excretion was not significantly different.. The three NSAIDs investigated did not neutralise the antihypertensive effect of the combination of lisinopril and HCT, and hence the blood pressure lowering action of the combination may not be prostaglandin dependent.

Topics: Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents, Non-Steroidal; Antihypertensive Agents; Blood Pressure; Diclofenac; Drug Interactions; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hypertension; Ibuprofen; Lisinopril; Middle Aged; Osteoarthritis; Sulindac; Treatment Outcome

Nonsteroidal antiinflammatory drugs (NSAID) are frequently reported to interfere with the blood pressure lowering actions of various antihypertensive medications. We studied 17 women with arthritis and hypertension who were receiving fosinopril and HCTZ, and administered sequentially in random order ibuprofen, sulindac, and nabumetone for 1 month each, with an intervening 2-week washout period between each treatment period. During the washout period, subjects received acetaminophen. Blood pressure at the end of 2 weeks of acetaminophen was compared with blood pressure after 1 month of treatment with each of the NSAID. Mean blood pressure was unchanged before and after all NSAID: 108 +/- 7 v 107 +/- 9 for nabumetone, 108 +/-9 v 108 +/- 9 for sulindac, and 108 +/- 8 v 107 +/- 9 for ibuprofen. The 24-h urinary sodium excretion was not significantly different. We conclude that the three NSAID did not neutralize the antihypertensive effect of the combination of fosinopril and HCTZ, and hence the blood pressure lowering action of the combination may not be prostaglandin dependent.

Topics: Acetaminophen; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Blood Pressure; Butanones; Creatinine; Dinoprostone; Diuretics; Drug Interactions; Drug Therapy, Combination; Female; Fosinopril; Glomerular Filtration Rate; Humans; Hydrochlorothiazide; Hypertension; Ibuprofen; Middle Aged; Nabumetone; Renal Plasma Flow; Sodium; Sodium Chloride Symporter Inhibitors; Sulindac; Thromboxane B2

A placebo-controlled, double blind crossover study of the non-steroidal anti-inflammatory drugs (NSAIDs) sulindac and diclofenac was conducted in 16 patients with essential hypertension that was controlled by treatment with a beta blocker, a diuretic or co-administration of both. In 4 cases, another antihypertensive agent (prazosin or verapamil) was also co-administered. In every patient, plasma creatinine concentration was less than 0.14 mmol/l (normal range 0.07-0.12 mmol/l). Sulindac and diclofenac were each given for 7 weeks. Diclofenac caused a decrease of borderline significance in plasma aldosterone concentration. Neither NSAID altered the mean values for systolic or diastolic blood pressure, body weight, plasma electrolyte concentrations, urate clearance, creatinine clearance or plasma renin activity. However, rises in plasma creatinine concentration and falls in creatinine clearance occurred during NSAID therapy in three individual subjects. No significant differences were observed in this study between the effects on renal function or blood pressure of sulindac and diclofenac, both of which appear not to interfere with the antihypertensive actions of beta blockers and diuretics.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Antihypertensive Agents; Blood Pressure; Creatinine; Diclofenac; Diuretics; Double-Blind Method; Drug Interactions; Female; Humans; Hypertension; Male; Middle Aged; Renin-Angiotensin System; Sulindac

Effect of non-steroidal anti-inflammatory drug (NSAID) on blood pressure (BP) control was evaluated in elderly hypertensive patients treated with calcium antagonist. The study was based on a randomized, crossover design to compare the effect of an NSAID, sulindac, with that of another NSAID, diclofenac sodium, in the hypertension treatment. The study was completed in six elderly female subjects (the average age: 66 +/- 3 year) whose systolic BP and diastolic BP were more than 160 mmHg and more than 95 mmHg, respectively. When BP was controlled by nifedipine (20 mg x 2 per day in slow releasing form) within normal limits, sulindac (100 mg x 3 per day) or diclofenac sodium (25 mg x 3 per day) was administered for a week. After one week-washout period, the other NSAID was substituted. Plasma and urinary variables were measured on the final day of each study period. The average systolic BP and diastolic BP and the entry of study were 167 +/- 5 mmHg and 93 +/- 5 mmHg, respectively. Nifedipine significantly decreased the systolic BP to 140 +/- 4 mmHg (p less than 0.02) and the diastolic BP to 84 +/- 4 mmHg (p less than 0.05). Addition of either sulindac or diclofenac sodium did not affect BP, whereas urinary PGE2 excretion and plasma renin activity were significantly inhibited. Plasma creatinine and electrolyte concentration were not changed by the NSAIDs. The results indicate that either sulindac or diclofenac sodium does not interfere with control of hypertension by a calcium antagonist, nifedipine in in elderly hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Blood Pressure; Diclofenac; Dinoprostone; Drug Therapy, Combination; Female; Humans; Hypertension; Kidney; Nifedipine; Sulindac

The effects of sulindac and indomethacin on the blood pressure response to labetalol were determined in well-controlled predominantly obese hypertensive patients (n = 26). A stabilized dose of labetalol alone was administered on weeks 1 and 3, and either indomethacin or sulindac was administered with labetalol on week 2, with cross-over to the other drug on week 4. Indomethacin and sulindac increased the sitting and standing systolic blood pressure (BP) to a statistically significant extent compared with placebo. The effects of indomethacin on systolic BP, diastolic BP, and weight were not significantly different from those with sulindac. Indomethacin but not sulindac produced minor increases in diastolic BP and weight compared with placebo.

Topics: Adult; Aged; Analysis of Variance; Blood Pressure; Body Weight; Chlorides; Drug Interactions; Humans; Hypertension; Indomethacin; Labetalol; Middle Aged; Obesity; Random Allocation; Sodium; Sulindac

Twenty-eight patients with mild to moderate essential hypertension well controlled by atenolol entered a five-week, double-blind, placebo-controlled trial of the effects of sulindac and naproxen on blood pressure (BP) control. Atenolol alone was administered during weeks 1, 3, and 5. Naproxen or sulindac was administered with atenolol during week 2, with crossover during week 4. Data were analyzed for 27 of the patients (one dropped out after developing a skin rash). Naproxen significantly increased the systolic BP compared with placebo (mean 4.0 mm Hg; 95 percent confidence interval, 1.1-7.0; p less than 0.05). There were no significant differences in systolic BP during sulindac administration compared with placebo or naproxen. No significant effects on diastolic BP were observed. Weight was increased by naproxen and sulindac compared with placebo (mean 0.6-0.8 kg, p less than 0.05), although not to a clinically significant extent. One-week therapy with naproxen has a greater potential than sulindac to increase systolic BP in well-controlled hypertensive patients receiving atenolol; however, the increase is minor and unlikely to be of clinical significance.

Topics: Adult; Aged; Atenolol; Blood Pressure; Body Weight; Double-Blind Method; Drug Interactions; Female; Humans; Hypertension; Male; Middle Aged; Naproxen; Sulindac

1. The effects of non-steroidal anti-inflammatory drugs (NSAID) on prostacyclin and thromboxane biosynthesis and on blood pressure were determined in 46 patients with mild essential hypertension. Patients who had abstained from antihypertensive therapy for 2 weeks before study were treated with either aspirin, ibuprofen, sulindac or placebo for 7 days. 2. Excretion rates of 2,3-dinor-6-oxo-prostaglandin (PG) F1 alpha, 6-oxo-PGF1 alpha, 2,3-dinorthromboxane (TX) B2 and TXB2 were measured as indices of prostacyclin and TXA2 biosynthesis. Samples were assayed using immunoaffinity chromatography and gas chromatography/electron capture chemical ionisation mass spectrometry. 3. Aspirin and ibuprofen reduced urinary excretion of all prostacyclin- and thromboxane-derived products. Sulindac inhibited excretion of 2,3-dinor-6-oxo-PGF1 alpha, 6-oxo-PGF1 alpha and 2,3-dinor-TXB2, but had no significant effect on TXB2. 4. Systolic blood pressure increased in the ibuprofen-treated group when compared with the placebo group. There were no other significant changes in systolic or diastolic pressure in any of the treatment groups. Among the patients as a whole, there was a significant negative correlation between change in blood pressure and change in excretion of the prostacyclin-derived but not of the thromboxane-derived products. 5. We conclude that, in patients with mild essential hypertension, neither sulindac nor aspirin (in the doses used) selectively spares prostacyclin biosynthesis by the kidney. The significant relationship between increase in blood pressure and reduction in prostacyclin biosynthesis favours the possibility that in individuals who become hypertensive, prostacyclin biosynthesis determines, in part, the severity of the hypertensive state.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Blood Pressure; Chromatography, Affinity; Epoprostenol; Female; Gas Chromatography-Mass Spectrometry; Humans; Hypertension; Ibuprofen; Kidney; Male; Middle Aged; Sulindac; Thromboxanes

Seventeen patients with hypertension and osteoarthritis participated in a single-blind crossover study comparing the effects of sulindac 200 mg twice daily, naproxen 500 mg twice daily, and placebo on blood pressure. All patients were treated for hypertension with propranolol monotherapy. Blood pressures were back-titrated to achieve a baseline diastolic blood pressure of 90 to 100 mm Hg while taking naproxen. There were no significant differences in mean sitting or standing blood pressures among the patients receiving naproxen, sulindac, or placebo treatments. There was no change in pulse, weight, or any of the laboratory measurements at the end of each treatment phase. These results suggest that neither sulindac nor naproxen interferes with propranolol therapy for uncomplicated hypertension.

Topics: Blood Pressure; Blood Urea Nitrogen; Body Weight; Clinical Trials as Topic; Creatinine; Drug Interactions; Humans; Hypertension; Indenes; Middle Aged; Naproxen; Potassium; Propranolol; Pulse; Random Allocation; Renin; Sodium; Sulindac

Twelve patients (mean age 48.8 years, 5 females) with untreated labile or mild essential hypertension completed a randomised, double-blind crossover study comparing the effects of two-week courses of indomethacin, sulindac and matching placebo upon sitting and standing blood pressure. Both indomethacin and sulindac significantly increased systolic BP when compared with placebo; indomethacin tended to have a greater pressor effect than sulindac. During treatment with indomethacin, the mean BP rose from 136/86 to 149/92 (sitting), and from 136/93 to 150/99 standing. The extent of the pressor response was unrelated to baseline BP. The results indicate that both non-steroidal anti-inflammatory drugs (NSAIDs) have a significant pressor effect in individuals with untreated labile or mild hypertension. The fact that sulindac had a pressor effect implies that this response may be unrelated to inhibition of renal prostaglandins, or that the renal-sparing effect of sulindac is only relative. Extra-renal prostaglandins may play a role in the control of BP in this population. Individuals with labile or mild hypertension do not appear to exhibit exaggerated pressor responses during treatment with these NSAIDs, as similar increases in BP have been reported in normal subjects.

Topics: Adult; Aged; Analysis of Variance; Blood Pressure; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Hypertension; Indomethacin; Male; Middle Aged; Random Allocation; Sulindac

The effects of enalapril alone and in combination with the cyclooxygenase inhibitors sulindac and indomethacin on blood pressure (BP), plasma aldosterone, renin activity and converting enzyme activity were evaluated in 29 patients with mild to moderate essential hypertension, 26 of whom had low plasma renin activity. Patients were randomly assigned to one of three treatment groups. All patients underwent a 4-week placebo phase (phase I), then received enalapril (20 mg BID) for 4 weeks (phase II). In phase III, group I (n = 10) continued on enalapril alone; group II (n = 9) received sulindac 200 mg BID plus enalapril, and group III (n = 10) received indomethacin 50 mg BID plus enalapril, all for 4 weeks. Enalapril lowered BP significantly (mean supine BP 149/100 in phase I vs. 134/90 in phase II, p less than 0.05) without inhibiting aldosterone production. The BP effect was not blunted by concomitant administration of sulindac or indomethacin. Enalapril lowered converting enzyme activity to 25% to 30% of baseline and tended to increase renin activity. In the 10 patients who received indomethacin (group III), the effects of enalapril alone and enalapril plus indomethacin on urinary excretion of 6-keto prostaglandin F1 alpha (PGF1 alpha), a stable metabolite of prostacyclin (PGI2), were examined. Enalapril increased urinary 6-keto PGF1 alpha in group III from 118 +/- 23 to 194 +/- 38 ng/g creatinine (p less than 0.05), while addition of indomethacin reduced 6-keto PGF1 alpha to basal levels (138 +/- 26 ng/g creatinine).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Aldosterone; Enalapril; Epoprostenol; Female; Humans; Hypertension; Indomethacin; Male; Middle Aged; Random Allocation; Renin; Sulindac

Twenty-five hypertensive patients participated in a randomized placebo-controlled study. After blood pressures were normalized with propranolol or verapamil alone over a 6-week period, patients were entered into a 4-week double-blind period where they received non-steroidal anti-inflammatory drug (NSAID) treatment (sulindac or piroxicam) or placebo treatment in addition to their antihypertensive therapy. There was a significant elevation in standing systolic blood pressure (P less than 0.05) with propranolol and sulindac, when compared with propranolol and placebo, but no significant changes were shown with propranolol and piroxicam. Systolic blood pressures on sulindac treatment were significantly lower (P less than 0.05) in both supine and standing positions during treatment of hypertension with verapamil compared with propranolol. Both supine systolic and diastolic blood pressures on piroxicam treatment were significantly lower (P less than 0.05) during treatment of hypertension with verapamil compared with propranolol. We conclude that NSAID transiently block the antihypertensive effect of propranolol, causing blood pressures to increase and side effects to improve. However, NSAID do not cause loss of antihypertensive control with verapamil.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Antihypertensive Agents; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hypertension; Male; Middle Aged; Piroxicam; Propranolol; Random Allocation; Sulindac; Verapamil

In an open triple crossover study in 8 patients with essential hypertension, the possibility has been investigated of whether the blood pressure lowering effect of hydrochlorothiazide 50 mg once daily was attenuated by co-administration for 4 weeks of ibuprofen 400 mg t.i.d., diclofenac 25 mg t.i.d. or sulindac 200 mg b.i.d. Only a slight, statistically nonsignificant change was found, with the exception of a significant increase in systolic blood pressure after 4 weeks treatment with ibuprofen. There was considerable variation in the blood pressure response during treatment with all three NSAIDs, with slight rises in blood pressure in 13 out of 24 periods. Body weight increased significantly on treatment both with ibuprofen and diclofenac, whereas the increase on sulindac was less and was transient. No significant change was found in various biochemical parameters, including plasma electrolytes, plasma renin activity (PRA), aldosterone, albumin and creatinine, in haematocrit or in the 24-h urinary excretion of sodium and potassium. The sole exception was a decrease in PRA during ibuprofen treatment. From these observations it is concluded that ibuprofen and diclofenac differ from sulindac in their interaction with the diuretic action of hydrochlorothiazide. It appears that all three NSAIDs can safely be combined with hydrochlorothiazide in hypertensive patients, but blood pressure should be monitored carefully when an NSAID are added.

Topics: Adult; Aged; Aldosterone; Blood Pressure; Clinical Trials as Topic; Creatinine; Diclofenac; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hypertension; Ibuprofen; Indenes; Male; Middle Aged; Potassium; Renin; Sulindac

The effect of sulindac on renal function and blood pressure was compared with those of placebo, piroxicam, and naproxen in 20 patients with primary hypertension being treated with a diuretic and a beta-blocker. Although the three non-steroidal anti-inflammatory drugs (NSAIDs) did not differ in their effect on renal function (weight, glomerular filtration rate, creatinine clearance) or on serum thromboxane and plasma 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha), blood pressure was significantly lower with sulindac than with placebo, piroxicam, or naproxen. These differences were associated with less renal cyclooxygenase inhibition by sulindac (reflected by urinary thromboxane B2 and 6-keto PGF1 alpha) than by other NSAIDs. The findings suggest that the blood pressure differences reflect vasodilation due to differences in the balance between systemic and renal effects of the NSAIDs.

Topics: 6-Ketoprostaglandin F1 alpha; Adrenergic beta-Antagonists; Adult; Amiloride; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Blood Pressure; Clinical Trials as Topic; Diuretics; Double-Blind Method; Drug Synergism; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hypertension; Indenes; Male; Middle Aged; Naproxen; Piroxicam; Random Allocation; Sulindac; Thiazines; Thromboxane A2; Timolol

Topics: Acetaminophen; Adult; Aged; Blood Pressure; Female; Humans; Hypertension; Indenes; Indomethacin; Male; Middle Aged; Sulindac

In this double-blind two period crossover study, we investigated the effect of indomethacin and sulindac on blood pressure in 25 hypertensive patients being treated with hydrochlorothiazide. The study consisted of seven 4 week periods. In the first and the last period the patients took placebos, in period two, four and six they were treated with hydrochlorothiazide 50 mg once daily alone, and in the third and fifth period hydrochlorothiazide 50 mg once daily was given in combination with either indomethacin 50 mg twice daily or sulindac 200 mg twice daily in double-blind random order. Blood pressure, measured by sphygmomanometer and arteriosonde, and body weight were determined every 2 weeks. Compared with placebo hydrochlorothiazide decreased the mean arterial pressure by 8%. Addition of both indomethacin and sulindac resulted in only slight and generally similar changes of this blood pressure lowering effect. This was found both for the whole group and when both treatment sequence groups were analysed separately. In contrast to sulindac, indomethacin attenuated the hydrochlorothiazide-induced decreases of body weight, plasma potassium and the increase of plasma renin activity. Both non-steroidal anti-inflammatory drugs (NSAID) reduced the 24 h urinary excretion of prostaglandins (PGs), i.e. PGF2 alpha, 6 ketoPGF1 alpha and thromboxane B2 except PGE2. From this study it can be concluded that, in contrast to sulindac, indomethacin attenuated the diuretic action of hydrochlorothiazide, however apparently without consequences for its long-term blood pressure lowering effect. This study does not support the hypothesis that the difference between the two NSAIDs can be explained by different effects on renal PG synthesis.

Topics: Adult; Aged; Blood Pressure; Clinical Trials as Topic; Diuresis; Double-Blind Method; Drug Interactions; Female; Humans; Hydrochlorothiazide; Hypertension; Indenes; Indomethacin; Kidney; Male; Middle Aged; Sulindac

Vasodilator prostaglandins produced in the renal medulla have a role in blood pressure regulation, beyond modulation of sodium and water retention. Systemic vasodilation resulting from effects of renomedullary prostaglandins lowers systemic vascular resistance, and administration of NSAIDs elevates blood pressure in hypertensive patients treated with diuretics and/or beta blockers, in patients with myocardial infarction, and in patients taking sympathomimetic agents such as phenylpropanolamine. Aspirin, which appears in the urine as salicylic acid (which has no effect on cyclooxygenase) has not been implicated as a drug which attenuates blood pressure control. Similarly, sulindac, the active sulfide metabolite of which is not filtered, does not inhibit renal synthesis of prostaglandins, though given in doses sufficient to inhibit serum thromboxane and 6-keto PGF 1-alpha. In a double-blind complete crossover study of blood pressure and renal function in hypertensive patients controlled with timolol-hydrochlorothiazide, sulindac lowered blood pressure significantly, whereas naproxen and piroxicam significantly raised blood pressure, in the absence of any effect on GFR, plasma renin, weight, creatinine clearance, or urinary sodium. It is suggested that for arthritic patients with hypertension, the NSAIDs of choice are aspirin and sulindac.

Topics: 6-Ketoprostaglandin F1 alpha; Anti-Inflammatory Agents, Non-Steroidal; Blood Pressure; Clinical Trials as Topic; Double-Blind Method; Humans; Hypertension; Kidney; Sulindac; Thromboxane B2

One hundred ten patients of both sexes with mild to moderate essential hypertension were studied in this double-blind, multicenter study. In the double-blind portion of this study, which covered weeks 11 to 14, 71 patients were evaluated to determine the effect of Clinoril (sulindac, MSD), piroxicam, and placebo on the hypotensive effect of propranolol. All 110 patients were considered for safety evaluation. Patients treated with propranolol alone were distributed randomly into three groups (Clinoril, piroxicam and placebo) and compared in a 15-week study with four periods (I through IV). Having fulfilled the criteria for hypertension (I) and having been successfully controlled with propranolol alone (II), patients were entered into a double-blind period (III) comparing the three drug treatments during four weeks followed by one week of propranolol alone (IV). During period III, patients treated with piroxicam had significantly greater (p less than 0.05) increases in supine and standing diastolic blood pressure than patients treated with Clinoril. No clinical difference was shown between patients treated with Clinoril and placebo. At the end of period IV patients treated with piroxicam maintained the increase in their diastolic blood pressure, in contrast to Clinoril and placebo where no clinical difference was noted. Significantly more patients treated with piroxicam than Clinoril had a 10 mmHg or greater increase of their supine diastolic blood pressure. These results show that Clinoril does not blunt the antihypertensive effect of propranolol in patients with mild to moderate hypertension in contrast to piroxicam. This is an extension of a report previously published in Advances in Therapy, Vol. 2, No. 4, July/August 1985.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Blood Pressure; Clinical Trials as Topic; Double-Blind Method; Humans; Hypertension; Indenes; Piroxicam; Propranolol; Random Allocation; Sulindac

Attenuation of the effectiveness of antihypertensive therapy by non-steroidal anti-inflammatory (NSAI) drugs has been attributed to inhibition of systemic or renal vasodilator prostaglandin synthesis, or a combination of both. Indomethacin is a NSAI drug with both renal and extrarenal cyclo-oxygenase inhibition properties. Sulindac is a relatively selective cyclo-oxygenase inhibitor said not to affect urinary prostaglandin excretion. This study examines the relative effect on blood pressure of 4 weeks' treatment, with indomethacin 25 mg three times daily and sulindac 200 mg twice daily, in a randomized placebo controlled trial in 26 hypertensive subjects. In nine patients treated with indomethacin, supine blood pressure rose 11 mmHg systolic and 4 mmHg diastolic by the end of the first week, whereas nine subjects treated with sulindac showed a fall in blood pressure similar to the trend seen in placebo-treated subjects. Indomethacin treatment inhibited renal cyclo-oxygenase with a 78% reduction in urinary prostaglandin E2 excretion and 89% suppression of plasma renin activity. Neither measurement was affected by sulindac. Extrarenal cyclo-oxygenase activity was inhibited by both indomethacin and sulindac with serum thromboxane B2 decreasing by 96% and 69% respectively. The results suggest that the pressor effect of NSAI drugs is predominantly related to renal cyclo-oxygenase inhibition. the lack of effect of sulindac on blood pressure may make it a safer therapeutic option if NSAI drug therapy is necessary in the hypertensive patient.

Topics: Adult; Aged; Blood Pressure; Cyclooxygenase Inhibitors; Female; Humans; Hypertension; Indenes; Indomethacin; Kidney; Male; Middle Aged; Prostaglandin-Endoperoxide Synthases; Renin; Sodium; Sulindac

Four placebo controlled, randomised crossover studies were carried out to investigate the effects of non-steroidal anti-inflammatory drugs and analgesics on blood pressure control in treated hypertensive patients. Twelve patients completed one study comparing indomethacin, 25 mg tds, with placebo in 2 six week phases; there were increases in mean blood pressure (p less than 0.01) of 9 mm Hg (casual), 8 mm Hg (supine) and 10 mm Hg (standing) in the indomethacin phase accompanied by a 50% reduction in plasma renin activity (p less than 0.05) and a 47% decrease in plasma aldosterone concentration (p less than 0.05). Similar studies on aspirin-SR, 650 mg daily (19 patients), and paracetamol, 1 g 8th hourly (20 patients), revealed only small changes in blood pressure, with a 2 mm Hg increase in supine diastolic blood pressure during aspirin therapy and a 4 mm Hg increase in supine and standing systolic blood pressure during paracetamol therapy (p less than 0.05 for both). Nineteen patients completed a study with 4 three week phases, taking placebo, naproxen 250 mg mane and 500 mg nocte, sulindac 200 mg bd, and aspirin-SR 1950 mg bd. All three active agents depressed plasma renin activity and plasma aldosterone concentration. Neither sulindac nor aspirin caused any significant increases in blood pressure, and naproxen had little effect, though it did cause a 4 mm Hg increase in standing systolic pressure (p less than 0.05). We conclude that the effects of indomethacin on control of blood pressure in treated hypertensive patients are not exhibited to the same extent by other drugs investigated, and that they are not dependent on the concomitant decreases in plasma renin activity or plasma aldosterone concentration. The importance of inhibition of prostaglandin synthesis remains unclear.

Topics: Acetaminophen; Aldosterone; Aspirin; Blood Pressure; Clinical Trials as Topic; Double-Blind Method; Heart Rate; Humans; Hypertension; Indenes; Indomethacin; Naproxen; Placebos; Random Allocation; Renin; Sodium; Sulindac; Time Factors

In an open triple crossover study in 10 patients with mild to moderate essential hypertension the influence was investigated of adding indomethacin 50 mg, naproxen 250 mg, or sulindac 200 mg, each twice daily for four weeks, to diuretic treatment with hydrochlorothiazide 50 mg a day. After two weeks' treatment with indomethacin a slight increase in blood pressure was observed, whereas both sulindac and naproxen tended to enhance the antihypertensive effect of hydrochlorothiazide. After treatment for four weeks, however, the effects of all three drugs on blood pressure appeared to be blunted. Furthermore, body weight increased significantly during treatment with indomethacin but not during treatment with naproxen or sulindac. No significant changes were found for various biochemical variables, including concentrations of plasma electrolytes and serum creatinine and albumin, plasma renin activity, plasma aldosterone concentration, and 24 hour urinary excretion of sodium and potassium, with the exception, however, of an increase in plasma potassium concentration during treatment with indomethacin. These observations suggest that the interaction of indomethacin, naproxen, and sulindac with diuretic treatment in mild to moderate essential hypertension is transient and of minor clinical importance.

Topics: Adult; Aged; Anti-Inflammatory Agents; Blood Pressure; Drug Interactions; Female; Humans; Hydrochlorothiazide; Hypertension; Indomethacin; Male; Middle Aged; Naproxen; Prospective Studies; Sulindac

Topics: Adrenergic beta-Antagonists; Anti-Inflammatory Agents, Non-Steroidal; Antihypertensive Agents; Blood Pressure; Diuretics; Humans; Hypertension; Sulindac

Topics: Blood Pressure; Blood Viscosity; Humans; Hypertension; Indenes; Indomethacin; Sulindac

Integrity of renal prostaglandin synthesis is necessary to maintain renal cortical and medullary function in patients with kidney, heart and liver disease. A comparison of the biochemical effects of various non-steroidal anti-inflammatory drugs (NSAIDs) necessitates that renal prostaglandin synthesis, as reflected by urinary immunoreactive prostaglandin excretion, be assessed with proper attention to problems created by seminal fluid contamination, inadequate chromatographic separation of samples, and largely unknown cross reactivities of systemic eicosanoid metabolites with antibodies raised against primary prostaglandins. Most, but not all, clinical studies support the observation that conventional doses of sulindac, administered orally, do not inhibit renal prostaglandin synthesis or alter renal function. Caution is in order, however, about the use of any NSAID, including sulindac at conventional dosage, in patients with severe liver disease as the plasma levels of sulindac sulfide are increased and prolonged compared to patients with normal hepatic function. Furosemide-induced natriuresis is probably not prostaglandin-mediated, in contrast to increased in renal blood flow and renin release. Some NSAIDs can attenuate the efficacy of antihypertensive therapy. Inasmuch as sulindac does inhibit systemic vascular prostacyclin production, its lack of hypertensive effect vis-a-vis other NSAIDs argues in favor of the importance of intrarenal prostaglandin-dependent mechanisms in mediating the hemodynamic effects of non-selective cyclooxygenase inhibitors.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arachidonic Acid; Arachidonic Acids; Coronary Disease; Female; Heart Failure; Hemodynamics; Humans; Hypertension; Kidney; Kidney Diseases; Liver Cirrhosis; Male; Middle Aged; Prostaglandins; Sulindac

Renal function and systemic hemodynamics were assessed in 10 hypertensive patients and in 10 age-matched normotensive subjects during control conditions (80 mEq of sodium/day) and after a salt load, either alone (480 mEq/day) or combined with indomethacin or sulindac. Indomethacin was used to induce ubiquitous inhibition of prostaglandin synthesis and sulindac to inhibit prostaglandin synthesis in all tissues except the kidney. Under control conditions there was no significant difference between the 2 groups in any measurement except blood pressure and total peripheral resistance. Also, the changes induced by salt load in the 2 groups were comparable. However, after indomethacin administration, only hypertensive patients showed a significant reduction in the 24-hour sodium excretion (from 417 +/- 61 to 317 +/- 49 mEq, p less than 0.05), so that the difference between this value and the corresponding value of normotensive subjects (453 +/- 79 mEq) became significant (p less than 0.05). The changes in sodium excretion in hypertensive patients were significantly correlated with the changes in renal plasma flow (r = 0.803, p less than 0.01). However, cardiac output and renal blood flow showed a similar pattern in normal and hypertensive persons. Finally, after the addition of sulindac to salt load, the differences in the 24-hour sodium excretion vanished. These results were also confirmed in an ancillary study performed, using the same protocol, in 10 other hypertensive patients using ibuprofen rather than indomethacin. Our data suggest that renal prostaglandins participate in renal disposal of chronic salt load in hypertensive patients but not in normal persons.

Topics: Adolescent; Adult; Blood Pressure; Cardiac Output; Diuresis; Female; Humans; Hypertension; Ibuprofen; Indomethacin; Kidney; Male; Middle Aged; Potassium; Prostaglandins; Sodium; Sodium Chloride; Sulindac; Vascular Resistance

Indomethacin and sulindac were used as tools to study the role of renal and/or systemic prostaglandins in the pharmacological response to atenolol. Patients receiving chronic treatment with atenolol 100 mg received indomethacin 50 mg twice daily or sulindac 200 mg twice daily in a randomised crossover trial. Indomethacin significantly reduced the antihypertensive action of atenolol while sulindac had no effect. The role that systemic and/or renal prostaglandins may play in the antihypertensive action of atenolol is discussed with reference to renal PGI2 production and inhibition of platelet cyclo-oxygenase.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Atenolol; Blood Pressure; Body Weight; Drug Interactions; Female; Humans; Hypertension; Indenes; Indomethacin; Male; Middle Aged; Random Allocation; Renin; Sulindac; Thromboxane B2

Topics: Benzothiadiazines; Blood Pressure; Diuretics; Drug Interactions; Humans; Hypertension; Indenes; Indomethacin; Male; Middle Aged; Sodium Chloride Symporter Inhibitors; Sulindac

Topics: Female; Humans; Hypertension; Indenes; Middle Aged; Prostaglandin Antagonists; Sulindac