Dose-related cardiovascular effects of spironolactone.

The aim of this study was to assess the short-term hemodynamic effects of increasing doses of spironolactone (25, 50, and 75 mg/day) on oliguric patients (5 men, mean age 47 +/- 12 years) undergoing hemodialysis for chronic renal impairment. Parameters of interest included heart rate (HR), cardiac output, systemic vascular resistance (SVR), arterial pressure, right atrial pressure, and pulmonary capillary wedge pressure (PCWP). The study also evaluated how spironolactone modified the effects on arterial and right atrial pressures and PCWP of infusion of increasing doses of norepinephrine (20, 40, and 100 ng/kg/min) and angiotensin II (2, 4, and 10 ng/kg/min). Compared with placebo, the lowest dose of spironolactone (25 mg/day) produced statistically significant (p < 0.05) modifications in systemic arterial pressures without a compensatory increase in cardiac output. The modifications were more pronounced at 50 and 75 mg/day, and the latter had a significant dose-dependent effect. Moreover, doses of 50 and 75 mg/day produced significant (p < 0.05) decreases in right atrial pressure and PCWP. Spironolactone administration caused the curve expressing the relation between an infused norepinephrine or angiotensin II dose and the blood pressure response to shift significantly (p < 0.05 to < 0.01) to the right, and the pressor doses of norepinephrine or angiotensin II showed a significant (p < 0.05 to < 0.01) dose-related increase, suggesting that treatment with spironolactone inhibited cardiovascular reactivity. This effect was observed on both the capacitance (i.e., low-pressure) and resistance (i.e., high pressure) vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

Long term effects of sustained release verapamil on the renal and systemic haemodynamic parameters in hypertensive patients with mild to severe chronic renal failure.

Calcium antagonists such as verapamil are among the antihypertensive agents categorised as first line treatments for essential hypertension. They have also shown efficacy in secondary forms of hypertension, including hypertension associated with chronic renal failure, irrespective of the degree of renal impairment. Systemic and renal haemodynamic parameters, and renal function were analysed in 15 hypertensive patients with mild to severe chronic renal failure after a 2-week placebo period and after 4 weeks of administration of verapamil sustained release (SR) 240 mg/day. After 4 weeks of treatment with verapamil SR, blood pressure was normalised in all patients. Arterial pressure decreased as a result of the decrease in systemic vascular resistance, while cardiac output and heart rate remained unchanged. Verapamil therapy did not significantly affect left cardiac function curves. The normalisation of arterial pressure did not result in changes in the glomerular filtration rate; however, renal vascular resistance decreased significantly, although the filtration fraction remained unchanged. Renal blood flow increased significantly and there was a significant increase in uricosuria and a subsequent decrease in plasma uric acid levels. In conclusion, verapamil SR is an effective and well tolerated treatment for hypertension associated with chronic renal failure.

Aldactazine/captopril combination, safe and effective in mild to moderate systemic hypertension: report on a multicenter study of 967 patients.

The safety and efficacy of a thiazide/potassium-sparing diuretic and an angiotensin-converting enzyme inhibitor used concomitantly was evaluated in a large, multicenter study. Aldactazine was administered alone for 2 months, after which time captopril was added in those whose blood pressure had not normalized (332 patients). At the end of the 6-month study, control of blood pressure was achieved in 88% of the patients with one or the other regimen. No clinically significant changes were recorded for a number of biologic parameters. Specifically, there was 1 case of hyperkalemia (6 mmol/liter), a very low incidence of hypotension (1.6%), and a low rate of adverse effects. Therefore, such a combination could provide important therapeutic benefits in hypertensive patients.

Effects of a potassium-sparing/thiazide diuretic combination on cardiovascular reactivity to vasopressor agents.

The vascular effects of a diuretic combination (spironolactone/altizide) were studied in 5 anuric patients undergoing dialysis by measuring changes in cardiovascular reactivity to norepinephrine (NE) and angiotensin II (AII) after infusion of incremental doses of these 2 vasopressor agents. There was a marked dose-response relation between NE and AII administration and mean (NE) or diastolic (AII) blood pressure (BP). Diuretic treatment moderated the increase in mean or diastolic BP induced by NE or AII. In addition, the pressor doses of NE and AII, which are also parameters of vascular reactivity, were significantly increased after diuretic treatment (NE, +101%; AII, +163%). Right atrial and pulmonary capillary wedge pressures increased along with BP in response to NE. Diuretic treatment also moderated the increase in right atrial and pulmonary capillary wedge pressures induced by NE. These results suggest that the antihypertensive action of spironolactone and altizide in combination is mainly due to a direct effect on resistance and capacitance vessels. The mechanisms by which diuretics modify the cardioreactivity remain poorly understood; however, they may modify electrolyte transport (sodium and calcium) across vascular smooth muscle cell membranes or stimulate prostaglandin release.

Association between sympathetic activity and the atherogenic serum cholesterol fraction.

A possible modulating influence of noradrenergic activity on serum lipoproteins was assessed under placebo conditions and following 4 weeks of sympathetic neurone blockade with debrisoquine in 9 normal subjects, 11 patients with mild essential hypertension, 9 normotensive, and 9 hypertensive hemodialysis patients. Plasma norepinephrine (NE) did not differ significantly among groups on placebo and was consistently reduced (P less than 0.05-0.001) by sympathetic blockade. The latter also decreased (P less than 0.05-0.001) plasma total cholesterol (C) as well as low and very low density lipoprotein cholesterol (LDL + VLDL-C) in the three patient groups. In the two dialysis groups, basal levels of plasma triglycerides (Tg) were increased and high density lipoprotein cholesterol (HDL-C) was diminished (P less than 0.01-0.001); sympathetic blockade lowered Tg and raised HDL-C (P less than 0.01-0.001). In normal subjects, sympathetic blockade did not significantly modify plasma lipoproteins. In the three patient groups, significant correlations (r = 0.62 - 0.88; P less than 0.05 - less than 0.001) existed between (a) basal plasma NE and total C or LDL + VLDL-C and (b) debrisoquine-induced changes in NE and changes in total LDL + VLDL-C. These findings suggest that in essential hypertension as well as in hemodialysis patients, the atherogenic C fraction, represented by LDL + VLDL-C, may be modulated by the noradrenergic activity.

Biocompatibility and hemodynamic studies during polycarbonate versus cuprophane membrane dialysis.

A new noncellulosic membrane (polycarbonate) has been tested in terms of biocompatibility and hemodynamic tolerance. The following results were obtained: The polycarbonate membrane manufactured by Gambro Hechingen induces activation of the complement system (slight decrease of CH50 and C3, no increase of C5a) to lower extent and causes a less severe leukopenia than the cuprophane membrane. During dialysis with the polycarbonate membrane hypoxemia does not occur and the pulmonary vascular resistances and pulmonary arterial pressure remain stable. The good biocompatibility of the polycarbonate membrane allows a better outcome of hemodialysis treatments.

Increased plasma ammonia may inhibit cellular release of branched-chain amino acids in systemic portal encephalopathy.

Plasma amino acid patterns were determined before and after hemofiltration (HF) and hemodialysis (HD) in 6 patients with portal systemic encephalopathy (PSE) and compared with the plasma AA patterns of 16 patients with chronic renal failure (CRF) treated either by HF or HD. The branched-chain amino acids (BCAA) increased paradoxically in PSE patients during HF but not with HD. There were no differences in BCAA's with HF as compared to HD in the CRF patients. The amount of amino acids lost was the same with both treatment modalities and in both patient groups. Much of the amino acids lost were released from the intracellular space. The BCAA release was significantly higher in PSE patients during HF. No correlation was found between plasma insulin, glucagon, and cortisol levels and BCAA release. An inverse correlation was found between the amount of BCAA's released from the intracellular space and the plasma ammonia levels. It is suggested that a selective cellular transport mechanism for BCAA exists which is inhibited by high plasma ammonia levels in PSE.

Correlation between plasma sodium acetate concentration and systemic vascular resistances.

Acetate in dialysis fluid induces during haemodialysis a fall in systemic vascular resistance. In patients with hepatic insufficiency, acetate concentrations are higher than in patients without hepatic insufficiency and in such patients vascular sensitivity to acetate is perhaps potentiated by modifications of acid base status. The close inverse correlations between acetate concentrations and systemic vascular resistance are strong indications that acetate is a major factor involved in the genesis of 'dialysis hypotension'.