Biomedical subjects

W D Reitsma

Publications and source records attributed to W D Reitsma.

At least 37 records · Page 2Linked to original sources

PubMed1996

Normal insulin release during sustained hyperglycaemia in hypokalaemic periodic paralysis: role of the potassium channel opener pinacidil in impaired muscle strength.

1. Hypokalaemic periodic paralysis is characterized by attacks of muscle weakness. Glucose, insulin and an abnormal regulation of ATP-sensitive potassium channels may be involved in these attacks. We studied the effect of hyperglycaemia and of the potassium channel opener pinacidil on insulin release and muscle strength in patients with hypokalaemic periodic paralysis. 2. Insulin release was assessed on two occasions in four patients with hypokalaemic periodic paralysis and in eight matched control subjects, with and without treatment with 25 mg pinacidil orally, during a hyperglycaemic glucose clamp at a blood glucose level of 10 mmol/l, in a placebo-controlled, double-blind study. Muscle strength was measured in the hypokalaemic periodic paralysis patients before and during hyperglycaemia using a handheld dynamometer. 3. During the clamp, the mean glucose concentration (10-180 min) in control subjects was 9.9 +/- 0.07 and 10.0 +/- 0.03 mmol/l with and without pinacidil respectively, and in patients with hypokalaemic periodic paralysis was 10.0 +/- 0.04 and 10.1 +/- 0.06 mmol/l respectively (not significantly different). In both groups, the areas under the insulin curve from 0 to 10 min (first-phase insulin release) and from 30 to 180 min (second phase) were not different on the pinacidil study day compared with on the placebo day. The areas under the insulin curve of the first and second phases also did not differ between control subjects and patients with hypokalaemic periodic paralysis (with or without pinacidil). The M/I ratio, a measure of insulin sensitivity, was not different in the two groups. On the placebo day, baseline muscle strength in patients with hypokalaemic periodic paralysis was 165 +/- 16 N for the hip abductors and 168 +/- 19 N for the knee flexors. During the period of hyperglycaemia on the placebo day, muscle strength did not decrease in either muscle group. On the pinacidil study day, an increase in muscle strength was found only in the two hypokalaemic periodic paralysis patients with the lowest mean muscle strength (< 150 N) on the placebo day. The two hypokalaemic periodic paralysis patients with a mean muscle strength on the placebo day > 150 N showed no increase in muscle strength with pinacidil. 4. Insulin secretion and sensitivity were normal in patients with hypokalaemic periodic paralysis. Hyperglycaemia during hyperglycaemic clamping did not provoke paralytic attacks and did not result in a decrease in muscle strength. The potassium channel opener pinacidil had no effect on insulin secretion in hypokalaemic periodic paralysis patients or in normal subjects. Pinacidil may enhance muscle strength in those hypokalaemic periodic paralysis patients who suffer partial paralytic attacks.

Adult↗

PubMed1996

Impaired suppression of plasma free fatty acids and triglycerides by acute hyperglycaemia-induced hyperinsulinaemia and alterations in high density lipoproteins in essential hypertension.

OBJECTIVES: Essential hypertension may be associated with abnormalities in free fatty acids (FFA) and triglyceride metabolism, which could lead to alterations in high density lipoproteins (HDL). Lecithin: cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) are key factors in the esterification of cholesterol and the subsequent transfer of cholesteryl ester from HDL towards triglyceride-rich lipoproteins. We compared baseline plasma lipids, HDL lipids, plasma LCAT and CETP activity as well as the lowering of plasma FFA and triglycerides by acute hyperglycaemia-induced hyperinsulinaemia in patients with essential hypertension and control subjects. SETTING: University Hospital, Groningen. SUBJECTS AND DESIGN: Eight patients with essential hypertension and eight control subjects were studied during a 3-h hyperglycaemic glucose clamp (blood glucose, 10 mmol L-1). MAIN OUTCOME MEASURES: Plasma insulin, FFA, triglycerides and HDL lipids, plasma LCAT and CETP. RESULTS: Baseline plasma FFA, total cholesterol and HDL cholesterol were not different between the groups, but plasma triglycerides tended to be higher in the hypertensive patients (P < 0.10). The baseline HDL free cholesterol content and the HDL free cholesterol/cholesteryl ester ratio were lower (P < 0.05 for both) in the hypertensive than in the control group. Although baseline plasma LCAT and CETP activity were not significantly different between the groups, the plasma LCAT/CETP ratio, reflecting the amount of active LCAT compared to that of CETP, was higher in the hypertensive patients (P < 0.05). In the combined subjects and in the hypertensive group, the HDL free cholesterol content was negatively related to plasma triglycerides and to the LCAT/CETP ratio, whereas this ratio was positively correlated with plasma triglycerides (P < or = 0.01 for all correlations). During a 3-h hyperglycaemic clamp (blood glucose 10 mmol L-1) plasma FFA and triglycerides decreased to a lesser extent (P < 0.02 and P = 0.05) and remained higher (P < 0.05 for both) in the hypertensive patients, despite similar plasma insulin levels. CONCLUSION: The action of insulin on FFA metabolism is impaired which is likely to contribute to higher plasma triglycerides in essential hypertension. In turn, higher triglycerides influence the HDL lipid composition, either directly or via an effect on the plasma LCAT/CETP ratio.

Acute Disease↗

PubMed1996

Phentolamine precludes inhibitory effect of the K+ channel opener pinacidil on insulin release.

The K+ channel opener pinacidil, in clinical use as an antihypertensive agent, acts by opening ATP-sensitive K+ channels in striated and smooth muscle cells. In vitro and in vivo studies have suggested that it also diminishes insulin secretion. Insulin secretion can be influenced directly--by acting on the ATP-sensitive K+ channels of the pancreas--or indirectly--by activation of the sympathetic nervous system, caused by vasodilation. Therefore we studied the effect of pinacidil on insulin release after intravenous glucose challenge during alpha-adrenergic blockade with phentolamine. We found, that phentolamine precludes the effect of pinacidil on glucose induced insulin release in healthy man. This finding suggests that the inhibitory effect of pinacidil on insulin release is indirect and due to activation of the sympathetic nervous system. The latter effect is caused by the antihypertensive action of pinacidil. However, the suggestion of others, that pinacidil inhibits insulin secretion secretion via a direct action on ATP-sensitive K+ channels can not be excluded.

Adrenergic alpha-Antagonists↗

PubMed1996

Lack of specific renal haemodynamic effects of different doses of dopamine after infrarenal aortic surgery.

Dopamine is administered frequently in the operating theatre and intensive care unit patients undergoing mechanical ventilation with the aim of specifically enhancing renal blood flow. In an uncontrolled, open study, we administered sequentially different doses of dopamine (0, 2, 4, 8 and 0 microgram kg-1 min-1) during a 1-h period each. Systemic haemodynamic and renal haemodynamic variables were measured simultaneously using a pulmonary artery catheter and radiopharmaceuticals, respectively. We studied seven haemodynamically stable patients (mean age 66 yr), with a serum creatinine concentration < 160 mumol litre-1, after elective infrarenal abdominal aortic reconstruction. All patients received extradural analgesia with bupivacaine and sufentanil, and none had a previous history of heart failure. Dopamine induced a dose-dependent increase in cardiac index which returned to baseline after cessation of the dopamine infusion. Glomerular filtration rate (GFR) increased with all doses of dopamine, whereas renal blood flow (RBF) increased significantly only with the 2- and 4-microgram kg-1 min-1 doses. However, the ratio RBF/cardiac output remained unchanged with the 2- and 4-microgram kg-1 min-1 doses, but decreased with 8 micrograms kg-1 min-1 from 14 (1.5)% to 10 (1.3)%. We conclude that dopamine increased RBF and GFR as a result of an increase in cardiac output.

Aged↗

PubMed1996

No deterioration of insulin secretion by the potassium channel opener pinacidil in essential hypertension.

Hypertension has been associated with hyperinsulinemia and insulin resistance. The elevations in plasma insulin are the apparent adaptation of the pancreatic beta cell to the resistance to insulin. Maintenance of normal insulin release is therefore of great importance for subjects with hypertension. The potassium channel opener pinacidil has antihypertensive properties. Pinacidil has been shown to inhibit Insulin release in vitro in isolated pancreatic beta cells. We therefore studied the acute effect of pinacidil on insulin secretion and insulin sensitivity in hypertensive and control subjects. The acute effect of pinacidil (25 mg, orally) on plasma insulin was studied during a hyperglycemic clamp (180 min, blood glucose 10 mmol/L) in 10 healthy volunteers and in 10 non-obese hypertensive patients in a randomised, placebo controlled double blind study. Fasting plasma insulin levels were 54.8 +/- 10.9 and 51.1 +/- 8.8 pmol/L in the control group and statistically significantly higher in the hypertensive group: 90.5 +/- 16.6 and 100.0 +/- 16.2 pmol/L (with and without pinacidil, respectively, both P < 0.02 vs control group). Plasma insulin levels rose to maximum levels of 246.7 +/- 44.6 and 267.2 +/- 56.2 pmol/L after 5 min in the control group (with and without pinacidil, respectively, NS) and to maximum levels of 248.9 +/- 37.3 and 238.0 +/- 39.1 pmol/L after 5 min in the hypertensive group (with and without pinacidil, respectively, NS). Areas under the insulin curve (AUCinsulin) of the first and second phase did not differ between the control and hypertensive group, with or without pinacidil. In the control and the hypertensive group separately no statistically significant effect of pinacidil on the mean glucose infusion rate/mean insulin level (M/I) ratio, a measure for insulin sensitivity, was shown. When both groups were taken together, an increase in the M/I ratio under the influence of pinacidil was found for the third hour of the clamp (P < 0.02). In conclusion, fasting insulin levels in the hypertensive subjects were significantly higher than in the control subjects. The potassium channel opener pinacidil did not influence insulin secretion in hypertensive patients and healthy controls. Pinacidil may have an enhancing effect on insulin sensitivity.

Adult↗

PubMed1995

Potassium channel modulation: effect of pinacidil on insulin release in healthy volunteers.

The effect of a potassium (K+) channel opener (pinacidil) on serum insulin levels and blood glucose levels was investigated in normal volunteers during glucose loading. An intravenous glucose load was used with and without oral pretreatment: pinacidil (25 mg) 11 hours and 1 hour before the 25-g glucose loading. Serum insulin, C-peptide, blood glucose, and plasma catecholamines were measured between t = 0 and t = 180 minutes. Pinacidil led to significantly lower insulin levels, especially in the first phase. Serum C-peptide levels were not significantly lowered, and glucose levels were not changed. Pinacidil inhibits the first phase of insulin release after glucose administration in healthy volunteers. These findings suggest that the safety of the drug regarding glucose tolerance, should be tested separately in patients with diabetes mellitus and essential hypertension.

Adult↗

PubMed1995

Clinical relevance of ATP-dependent potassium channels.

Many cells are equipped with so-called potassium (K+) channels which have an important role in maintaining transmembrane potential. Closure of these channels leads to membrane depolarization, which can be followed by cell-specific activity such as contraction of vascular smooth muscle, or secretion of insulin from pancreatic beta-cells. Therefore, it is not surprising that a number of drugs have been introduced which influence K+ channels by either blocking or opening them. The treatment of type 2 (non-insulin-dependent) diabetes mellitus with sulphonylurea derivatives (SU), which exert their insulinotropic effect by closing the K+[ATP] channels of the pancreatic beta-cell, is customary. Slight differences are described in the insulinotropic action of the various SU. Claims in the past that treatment with SU increases cardiovascular mortality are not supported by sound evidence. SU may even reduce cardiovascular mortality by protecting against ventricular arrhythmias during cardiac ischaemia. K+[ATP]-channel-opening drugs are under investigation for the treatment of essential hypertension and angina pectoris. They are at least as effective in achieving adequate blood pressure control as calcium channel blockers. The recently introduced coronary vasodilating drug, nicorandil, exerts its effect by two mechanisms of action: opening K+[ATP] channels in vascular smooth muscle cells of coronary arteries and activation of guanidyl cyclase by its nitro-group in these cells. A proarrhythmic effect of K+[ATP] channel openers has only been observed at very high doses, but not in the low doses used in angina pectoris and hypertension. In vivo no negative effect of K+[ATP]-channel-opening drugs on insulin secretion is found.

Adenosine Triphosphate↗

PubMed1995

The effects of ibopamine on glomerular filtration rate and plasma norepinephrine remain preserved during prolonged treatment in patients with congestive heart failure.

UNLABELLED: In acute studies ibopamine, an a selective dopamine agonist, induces moderate increases of GFR and ERPF, and a fall in plasma norepinephrine levels in patients with congestive heart failure (CHF). We evaluated acute and chronic effects of ibopamine on renal haemodynamics, sodium excretion, PRA, plasma aldosterone (ALD) and norepinephrine levels in an open controlled study in 10 patients aged (51-79 years) with mild CHF, NYHA class II-III. All patients used digoxin and frusemide. After a control study day, the second study day involved the administration of 100 mg ibopamine. Subsequently the patients continued to take ibopamine 100 mg three times daily for one month, at which time the chronic effects were measured on the third study day. RESULTS: On the second day ERPF rose from a baseline of 288 +/- 32 to a mean of 308 +/- 32 ml.min-1 x 1.73 m-2 (P < 0.05) during the 4 h after the first administration of ibopamine and GFR rose from 77 +/- 8 to a mean of 84 +/- 8 ml.min-1 x 1.73 m-2 (P < 0.05). The ratio GFR/ERPF, representing the filtration fraction (FF) remained unchanged. On the third study day GFR and ERPF at baseline were similar to those before ibopamine treatment. After the acute on chronic administration we observed an increase in GFR (from 76 +/- 6 to a mean of 85 +/- 7 ml.min-1 x 1.73 m-2 (P < 0.05)), and in ERPF (from 279 +/- 27 to a mean of 293 +/- 29 ml.min-1 x 1.73 m-2 (P < 0.05)). Plasma norepinephrine levels fell from 2.63 +/- 0.48 to 1.92 +/- 0.27 nmol.l-1 (P < 0.05) after the acute administration of ibopamine, and remained unchanged after the acute on chronic ibopamine administration (C: 1.80 +/- 0.42 nmol.l-1). No changes in sodium excretion were observed, either in blood pressure, heart rate, PRA or ALD. We conclude that renal function is preserved during chronic ibopamine treatment and the acute moderate increase of ERPF and GFR after a single dose of 100 mg of ibopamine is still present after one month of treatment with ibopamine in patients with CHF. Ibopamine lowered plasma norepinephrine levels in our patients with CHF, and these values remained unchanged after the acute on chronic administration of ibopamine.

Adult↗

PubMed1995

Renal and systemic hemodynamic effects of ibopamine in patients with mild to moderate congestive heart failure.

To study the hemodynamic and renal effects of the orally (p. o.) active dopamine (DA) agonist ibopamine, we examined 10 patients with mild to moderate congestive heart failure (CHF), who were stable while treated with digoxin and diuretics. All patients were in New York Heart Association (NYHA) functional class II-III; their mean age was 63 years (range 51-79 years), and mean left ventricular ejection fraction (LVEF) was 28% (range 18-36%). The protocol consisted of a control study-day with measurements of renal characteristics including glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and filtration fraction (FF). One week later, systemic and renal hemodynamics were measured simultaneously before and after patients received one 100-mg tablet of ibopamine. Ibopamine caused a slight but significant increase in both ERPF (from 288 +/- 32 ml/min/1.73 m2 at baseline to 316 +/- 32 ml/min/1.73 m2 after ibopamine) and GFR (from 77 +/- 8 to 85 +/- 8 ml/min/1.73 m2; both p < 0.05); FF was not affected (mean value 0.26 +/- 0.02). Sodium excretion was not influenced by ibopamine, but diuresis increased significantly. Cardiac output (CO) increased significantly (from 4.0 +/- 0.4 L/min at baseline to a maximum of 5.0 L/min after ibopamine, p < 0.05), mainly due to decreased systemic vascular resistance (SVR). Heart rate (HR) and blood pressure (BP) were unchanged throughout the studies. The percentage of contribution of CO to renal blood flow (RBF) was not significantly affected by ibopamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1995

The effects of different doses of dopamine and domperidone on increases of plasma norepinephrine induced by cold pressor test in normal man.

The effect of dopamine 1 and 3 micrograms/kg/min i.v., of dopamine 1 and 3 micrograms/kg/min i.v. combined with domperidone 30 mg per os and of placebo infusion on plasma norepinephrine concentration before and during sympathetic stimulation by a cold pressor test was investigated in 10 healthy volunteers (1 female, 9 males, mean age 28, range 19-41). Dopamine 1 microgram/kg/min resulted in a blunting of the rise in plasma norepinephrine concentration during the cold pressor test, compared with placebo infusion. The addition of domperidone to dopamine 1 microgram/kg/min abolished this effect. Plasma norepinephrine levels during dopamine 3 micrograms/kg/min infusion, both with and without domperidone, were not different from placebo, but significantly higher compared to dopamine 1 microgram/kg/min infusion. Dopamine 1 and 3 micrograms/kg/min infusion, both with and without domperidone resulted in a blunted increase in blood pressure compared to placebo infusion. Dopamine 1 microgram/kg/min infusion resulted in a lower systolic blood pressure during the cold pressor test compared to dopamine 3 micrograms/kg/min infusion. No significant changes in heart rate occurred during the cold pressor test comparing the different circumstances. We conclude that in healthy volunteers only dopamine 1 microgram/kg/min, but not dopamine 3 micrograms/kg/min, blunts the increase in plasma norepinephrine concentration during a cold pressor test; this effect is abolished by pretreatment with domperidone. We presume that for dopamine 1 microgram/kg/min the inhibitory effects of presynaptic DA-2 receptor or alpha-2 adrenoceptor stimulation on plasma norepinephrine concentration predominate. When dopamine 3 micrograms/kg/min is infused, the inhibitory effects might be counteracted by uptake-1 inhibition or enhanced synthesis and release of norepinephrine, either directly or indirectly.

Adult↗

PubMed1995

Influence of ambient plasma noradrenaline on renal haemodynamics in type 1 (insulin-dependent) diabetic patients and healthy subjects.

Imbalances in renal vasodilatory and vasoconstrictive mechanisms are responsible for the renal haemodynamic changes observed in Type 1 diabetes mellitus. Animal experiments have shown that noradrenaline (NA) infusion increases the intraglomerular pressure by predominantly efferent arteriolar vasoconstriction. The relationships between ambient plasma NA levels and renal haemodynamics were studied in 18 healthy control subjects (group C); in 17 normoalbuminuric diabetic patients (group D1) (albumin excretion rate (Ualb V) < 20 micrograms min-1), and in 17 microalbuminuric Type 1 diabetic patients (group D2) (UalbV 20-200 micrograms min-1), all patients being without overt autonomic neuropathy. Supine glomerular filtration rate (GFR (ml min-1 1.73 m-2)) and effective renal plasma flow (ERPF (ml min-1 1.73 m-2)) were determined over a 2-h period using constant infusions of 125I-iothalamate and 131I-hippuran, respectively. The subjects were studied in the fasting state. The diabetic patients were investigated during near normoglycaemia. Data are given as means and SD. In group D1, GFR and ERPF (126 +/- 15 and 538 +/- 89, respectively) were elevated as compared with controls (108 +/- 15 and 478 +/- 73; p < 0.01 and p < 0.05, respectively). In group D2, GFR (124 +/- 25, p < 0.05) but not ERPF (515 +/- 104) was higher than in the controls. GFR and ERPF were negatively correlated with venous plasma NA in group C (r = -0.61, p < 0.005 and r = -0.64, p < 0.001, respectively), in group D1 (r = -0.54, p < 0.03 and r = -0.63, p < 0.005, respectively) and in group D2 (r = 0.53, p < 0.03 and r = -0.60, p < 0.01, respectively). Multiple regression analysis disclosed that diabetes per se, independent from plasma NA, had a positive contribution to GFR. In contrast, ERPF was only related to plasma NA levels. GFR and ERPF are inversely related to venous plasma NA levels, both in healthy and in diabetic subjects, supporting the hypothesis that plasma NA is a vasoconstrictive substance. The independent positive effect of diabetes as a categorial variable on GFR, suggests that concomitant vasodilating mechanisms play a role in the renal haemodynamic alterations in Type 1 diabetes mellitus.

Adult↗

PubMed1993

Potassium channels in hypokalaemic periodic paralysis: a key to the pathogenesis?

1. A possible role for the ATP-sensitive potassium channels in the pathogenesis of hypokalaemic periodic paralysis was investigated. 2. We assessed insulin release and muscle strength after intravenous glucose loading with and without the potassium channel opener pinacidil and the potassium channel blocker glibenclamide in three patients with hypokalaemic periodic paralysis and in a pair of matched control subjects for each patient. 3. A significantly higher initial insulin response (1.5-30 min) was found in the patients with hypokalaemic periodic paralysis in comparison with the control subjects. During potassium channel blocking with glibenclamide the insulin release was more enhanced in patients than in control subjects. On the other hand, the potassium channel opener pinacidil impaired the insulin release in healthy control subjects but not in patients. The serum glucose levels showed no differences between patients and control subjects. In one of the patients with hypokalaemic periodic paralysis glucose loading resulted in a fall in muscle strength, which did not occur during the administration of pinacidil. 4. These findings suggest a disturbance in the ATP-sensitive potassium channel in patients with hypokalaemic periodic paralysis, which is not limited to pancreatic beta cells, but may be also involved in the abnormal behaviour of skeletal muscle.

Adult↗

PubMed1993

Effects of ibopamine on renal haemodynamics in patients with severe congestive heart failure.

The effects of a single dose of ibopamine on renal haemodynamics, sodium excretion, blood pressure (BP) and heart rate (HR) were investigated in 10 patients (aged 52-82 years) with severe congestive heart failure (CHF) who were in NYHA class IV. All patients used ACE inhibitors, digoxin and diuretics. After determining baseline values, ibopamine 100 mg was administered. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured simultaneously using radio pharmaceuticals. An increase in GFR and ERPF was observed during 3 and 2 h, with a maximum of 15 and 11%, respectively. The ratio GFR/ERPF representing the filtration fraction (FF) was markedly elevated at baseline, 34%, and remained unchanged. No clinically significant increase of sodium excretion was found. No changes in blood pressure, heart rate, plasma renin activity (PRA) and aldosterone or norepinephrine were observed. We conclude that ibopamine increases both ERPF and GFR in patients with severe CHF, possibly as a consequence of both inotropic cardiac and specific renal effects with equal preglomerular and postglomerular vasodilation. The lack of the presumed fall in FF may be the consequence of the expected DA1-induced renal vasodilation, partially reversed by the alpha adrenergic properties of ibopamine for this dose. Ibopamine caused no clinically significant natriuresis in these salt-depleted patients. No changes in PRA, aldosterone and catecholamines were found.

Aged↗

PubMed1992

Effects of ibopamine on exercise-induced increase in norepinephrine in normal men.

The effects of 100 mg ibopamine, an orally active aselective dopamine (DA) agonist, on plasma catecholamines was evaluated in 8 healthy men during sympathetic stimulation by graded exercise in a single-blind, placebo-controlled cross-over study. The exercise consisted of progressive cycling activity less than or equal to 90% of the previously determined VO2max. Graded exercise resulted in an increase in systolic and mean blood pressure (SBP, MBP), heart rate, norepinephrine (NE) and epinephrine level, with a decrease in diastolic BP (DBP). The increase in NE was significantly blunted by ibopamine as compared with placebo. No differences for BP, heart rate (HR), or epinephrine between placebo- and ibopamine study day were noted. In previous studies, ibopamine decreased resting plasma NE in patients with congestive heart failure (CHF), whereas plasma NE was not altered by ibopamine in healthy volunteers. This different outcome in both categories might therefore be explained by the absence of substantial sympathetic stimulation in normal humans at rest. Because it is reasonable to assume that the effect of ibopamine on systemic and local hemodynamics is negligible as compared with the effect of exercise in the healthy volunteers, the plasma decrease caused by ibopamine is probably related to stimulation of DA2-receptors. In conclusion, ibopamine blunts the increase of plasma NE during graded exercise in healthy men.

Adult↗

PubMed1991

The effects of alpha-adrenoceptor blockade on dopamine-induced renal vasodilation and natriuresis.

To establish the effects of alpha-adrenoceptor blockade on dopamine-induced changes in renal hemodynamics and sodium excretion, dopamine dose-response curves were performed without and with pretreatment with the selective postsynaptic alpha 1-adrenoceptor antagonist prazosin in normal volunteers and in patients with renal disease and moderately impaired renal function. Prazosin (1 mg p.o. every 4 h) in 7 volunteers did not significantly affect baseline values but impaired the response of effective renal plasma flow (ERPF) and filtration fraction (FF) to infusions of dopamine in doses ranging from 0.5 to 8 micrograms/kg per minute and completely abolished the dopamine-induced increase in sodium excretion. In 7 patients with renal disease and a glomerular filtration rate (GFR) ranging from 38-85 ml/min pretreatment with prazosin did not affect baseline ERPF, GFR or FF or their response to dopamine infusion, but sodium excretion and its response to dopamine infusion were reduced (fractional excretion of sodium at baseline 1.78 without and 0.89 with prazosin pretreatment). We conclude that alpha 1-adrenoceptor blockade with prazosin abolishes the effects of exogenous dopamine on sodium excretion in normal man. Prazosin also impairs the renal vasodilatory action of dopamine. However, the effect on sodium excretion is not directly related to inhibition of dopamine-induced renal vasodilation since in patients with renal disease prazosin also markedly reduces sodium excretion but does not influence the renal hemodynamic effects of dopamine.

Adult↗

PubMed1991

Renal and neurohumoral effects of ibopamine and metoclopramide in normal man.

The effects of 100 mg ibopamine, an orally active nonselective dopamine agonist on renal haemodynamics, sodium excretion, blood pressure (BP), heart rate (HR) and neurohumoral parameters were investigated in 10 healthy volunteers, with and without metoclopramide pretreatment. A small and temporary rise of glomerular filtration rate (GFR) was found after ibopamine without but not with metoclopramide pretreatment. No differences in effective renal plasma flow (ERPF) but a small rise in sodium excretion were observed comparing ibopamine with control. Metoclopramide induced a fall in sodium excretion which was not reversed by ibopamine. Ibopamine failed to affect BP and HR and no changes of PRA or plasma aldosterone concentration (PAC) were found. Metoclopramide induced a pronounced increase of PAC which was blunted by ibopamine. Plasma and urinary catecholamines were unchanged for all study days. We conclude that ibopamine induces natriuresis probably not by the observed small and temporary renal haemodynamic effects but by direct stimulation of DA1 dopamine receptors in the proximal tubule.

Adolescent↗

PubMed1990

Dissociation of renal vasodilator and natriuretic effects of dopamine during sulpiride infusion in normal man.

The effect of sulpiride on dopamine-induced changes in renal function in man has been investigated. Dopamine dose-response studies were performed in 7 healthy volunteers before and after sulpiride 200 mg i.v. The same investigations were performed in 15 healthy volunteers after pretreatment with the selective alpha-1-adrenoceptor antagonist prazosin (n = 7) and the non-selective alpha-adrenoceptor-blocker phentolamine (n = 8). Infusion of dopamine 0.25 to 8 micrograms.kg-1.min-1 resulted in a dose-dependent increase in effective renal plasma flow (ERPF) and glomerular filtration rate (GFR), and a fall in filtration fraction (FF) in 7 normal volunteers. Sulpiride had no effect on base-line ERPF or GFR and did not influence the dopamine-induced renal vasodilatation in those volunteers. It did cause a fall in the fractional sodium excretion (FENa+%) from 1.7 to 1.38, and shifted the dose-response curve of the natriuretic response to a subsequent infusion of dopamine. Sulpiride enhanced the fall in diastolic blood pressure during infusion of dopamine. In 7 other volunteers pretreated with prazosin, sulpiride did not influence base-line ERPF, GFR or FF or their response to dopamine, but the sodium excretion fell markedly (FENa+% changed from 1.13 to 0.63). Administration of sulpiride to 8 volunteers after phentolamine pretreatment 20 mg.h-1 i.v. in the first hour followed by 10 mg.h-1 i.v. resulted in a fall in sodium excretion (FENa+% from 1.09 to 0.53) without affecting ERPF or FF, and it did not affect the dose-response curve in the subsequent DA infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Lack of effect of lithium on the renal response to DA1-dopamine receptor stimulation by fenoldopam in normal man.

1. The effect of oral lithium (300 mg) on the renal response to the selective DA1-dopamine receptor agonist fenoldopam was investigated in seven normal men. Lithium had no influence on sodium excretion and renal haemodynamics during fenoldopam infusion. The fenoldopam-induced rise in PRA was enhanced in the presence of lithium. We conclude that a previously described interaction between lithium and the dopamine agonist gludopa is not mediated by DA1-dopamine receptors or is confined to higher doses of lithium.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗