Acute sodium loading in patients with uncomplicated diabetes mellitus: renal and hormonal effects.

1. Diabetes mellitus is associated with high body sodium, but the pathogenetic mechanism is still unknown. The possibility that an abnormal renal handling of sodium, an abnormal responsiveness of sodium-modulating factors or a shift in the set point for sodium metabolism may contribute to or be associated with sodium retention was tested with an acute saline infusion. 2. A consecutive sample of 33 patients with stable non-azotaemic diabetes mellitus (24 insulin-dependent patients) and 30 normal control subjects was studied. Two litres of a 0.9% NaCl infusion were infused over 4 h. The urinary sodium excretion during the infusion and the next 18 h was analysed in relation to blood pressure, creatinine and lithium clearances, Na(+)-K+ co-transport, Na(+)-Li+ countertransport, plasma levels of renin, angiotensin II, aldosterone, noradrenaline, adrenaline, atrial natriuretic factor and digoxin-like factor. 3. Diabetic patients and control subjects did not differ in blood pressure, body mass index, clearances of creatinine, sodium or lithium, intracellular sodium Na(+)-K+ co-transport and Na(+)-Li+ countertransport, urinary and plasma levels of digoxin-like factor, plasma renin activity, angiotensin II, aldosterone, noradrenaline, adrenaline and atrial natriuretic factor. The intravenous saline infusion caused a similar natriuresis in diabetic patients and normal subjects; the renin-angiotensin-aldosterone system was suppressed to a higher degree in diabetic patients than in normal subjects, whereas atrial natriuretic factor was stimulated to a similar extent; plasma digoxin-like activity was unchanged in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium antagonists for treatment of diabetes-associated hypertension. Metabolic and renal effects of amlodipine.

In hypertensive diabetics a strict blood pressure control may decrease the incidence of cardiovascular and diabetic complications. Long-term experience with the use of calcium antagonists is still limited. The metabolic and renal effects of long-term (8 months) therapy with amlodipine, 5 to 10 mg daily, were studied in 15 hypertensive patients with uncomplicated diabetes mellitus as compared with 15 patients with essential hypertension. After a 4 week placebo phase, the diabetics and essential hypertensive patients did not differ in mean blood pressure (156/93 +/- 16/7 v 150/95 +/- 9/5 mm Hg), body weight, creatinine clearance, microalbumin excretion, and C-peptide and lipid levels, while serum fructosamine was higher in the diabetics. In both groups, amlodipine caused a significant and long-lasting decrease of arterial pressure (8%), but did not modify creatinine clearance, microalbumin excretion, and serum lipid levels. In diabetics indices of diabetic control and the insulin and glucose response to an oral glucose tolerance test were unchanged, whereas in essential hypertension the insulin response to a glucose load was decreased (P = .033). Amlodipine exerts a comparable and long-lasting antihypertensive effect in hypertensive diabetics and patients with essential hypertension. Despite the significant decrease in arterial pressure, there was no change in urinary microalbumin excretion. Lipid metabolism, quality of diabetic control, and the insulin response to a glucose load were not affected unfavorably.

[Smoking, blood pressure and body weight in the Swiss population: MONICA study 1988-89]. / Tabakkonsum, Blutdruck und Körpergewicht in der Schweizer Bevölkerung: MONICA-Studie 1988-89.

Two Swiss regions, the cantons of Vaud and Fribourg (VD-FR) and the canton of Ticino (TI), take part in the international research project MONICA (MONItoring trends and determinants in CArdiovascular disease). In this framework, three surveys are planned to monitor the prevalence of the principal risk factors. The second survey was carried out in 1988/89 on 2011 participants aged 25 to 74 for the VD-FR region and on 1458 participants aged 35 to 64 for the TI region. This article is devoted to the results concerning smoking habits, blood pressure, body height and weight. In the VD-FR region, the percentage of regular smokers steadily decreases with age, from 44% for men and 36% for women in the 25-34 age group to 15% and 10% respectively in the 65-74 age group. Inversely, the proportion of participants with high blood pressure rises steeply with age from nearly zero in the 25-34 group to more than a quarter in the 65-74 group. Similar risk factor levels are observed in the TI region. Two significant trends show up in comparison with the first survey (1984-86) for the latter region: the decreases in mean blood pressure levels for both sexes and in the proportion of regular smokers for men. However, these trends are to be interpreted cautiously because of potential measurement bias between surveys.

[Cardiac interactions between ketanserin and the calcium antagonist nifedipine]. / Kardiale Interaktionen zwischen Ketanserin und dem Calcium-Antagonisten Nifedipin.

Ketanserin and calcium antagonists are frequently used for the treatment of arterial hypertension in the elderly. The possibility that combined treatment with ketanserin and the calcium antagonist nifedipine have a pro-arrhythmic effect was investigated in 20 normal volunteers aged > 60 years with normal or slightly elevated blood pressure. Each subject received monotherapy with ketanserin or nifedipine for 1 week and the combined treatment during the following week. Clinical and biochemical parameters, ECG and 24-hour ECG recording were monitored before and at the end of the first and second treatment weeks. Ketanserin and nifedipine given in monotherapy or in combination did not modify, on average, blood pressure, heart rate, the biochemical variables and the QT interval. In the 24-hour ECG recordings, 2 normal subjects developed a marked increase in the frequency of ventricular ectopics, couplets and ventricular tachycardia after combined treatment. Therefore, the present investigation does not exclude the possibility that combined treatment with ketanserin and nifedipine could increase the prevalence of arrhythmia in some elderly patients.

Antihypertensive mechanism of amlodipine in essential hypertension: role of pressor reactivity to norepinephrine and angiotensin II.

Calcium entry blockade may affect the pressor reactivity to vasoconstrictors. The pressor response to norepinephrine and angiotensin II, as well as several other blood pressure modulating factors, were studied in normal subjects (n = 9) and patients with essential hypertension (n = 10) before and after 8 weeks of treatment with the long-acting dihydropyridine amlodipine. In control subjects, calcium entry blockade did not modify blood pressure, the pressor and aldosterone response to angiotensin II, the activity of the renin-angiotensin and sympathetic nervous systems, or urinary dinoprostone (prostaglandin E2) excretion; however, the pressor response to norepinephrine was significantly decreased (p less than 0.01). In patients with hypertension, amlodipine decreased blood pressure (p less than 0.01) and the pressor response to both norepinephrine and angiotensin II (p less than 0.01), without changes in body weight, plasma renin, angiotensin II and catecholamine levels, dinoprostone excretion, or aldosterone responsiveness to angiotensin II. These findings suggest that calcium entry blockade modifies sympathetic-dependent vasoconstriction in both normal subjects and in patients with hypertension. Angiotensin II pressor response may be selectively decreased in essential hypertension.

Swiss hypertension treatment programme with verapamil and/or enalapril in diabetic patients.

The purpose of the present study was to assess the efficacy and tolerability of diuretic-free antihypertensive therapy with a calcium antagonist and/or an angiotensin converting enzyme (ACE) inhibitor in patients with diabetes mellitus. 54 hypertensive [blood pressure (BP) above 140/90mm Hg] patients with diabetes mellitus type 1 (n = 7) or 2 (n = 47) and normal serum creatinine levels (mean 82 +/- 6 mumol/L) received either verapamil or enalapril after a 2-week washout and a 4-week placebo phase. If BP remained elevated, both agents were combined. Verapamil or enalapril alone normalised diastolic BP (to less than 90mm Hg) in 36 patients; verapamil decreased BP from 159/98 to 147/87mm Hg (n = 19, p < 0.001) and enalapril decreased BP from 166/99 to 146/88mm Hg (n = 17, p < 0.001). In 18 patients who remained hypertensive after 10 weeks of monotherapy, a combination of both drugs decreased BP from 169/104 to 151/90mm Hg (p < 0.001). Overall, 87% of patients achieved a target BP response at 30 weeks. Urinary albumin as related to creatinine excretion (UAE; micrograms albumin:mg creatinine) was on average not significantly changed after verapamil or enalapril treatment, alone or combined. Nevertheless, in patients with initial microalbuminuria, UAE decreased (p < 0.05) during enalapril treatment. Serum potassium, total lipids, high density lipoprotein cholesterol, low density lipoprotein cholesterol, glycosylated haemoglobin, serum C peptide and fructosamine levels were not significantly modified by treatment. Subjective tolerability of the drugs was also generally good. Thus, in hypertensive patients with diabetes, a diuretic-free therapy based on the calcium antagonist verapamil or the ACE inhibitor enalapril, alone or combined, can effectively decrease BP without adversely affecting carbohydrate and lipid metabolism.

Lithium clearance in patients with chronic renal diseases.

The clearance of lithium was analyzed in relation to the glomerular filtration rates and the effective renal plasma flow in 41 patients with renal disease and variable degree of renal functional impairment and in 40 normal subjects. In the patients, there was on average a 35% decrease of glomerular filtration rates (109 +/- 64 [SD] ml/min) and renal plasma flow (490 +/- 275 ml/min) and a 25% decrease of lithium clearance (22 +/- 12 ml/min); the lithium clearance correlated closely with the glomerular filtration rates and renal plasma flow (r = 0.69; p less than 0.001). The absolute proximal reabsorption of fluid was decreased by 38% (89 +/- 56 ml/min) while the distal absolute reabsorption of sodium (21 +/- 12 ml/min) was unchanged. Individual values of fractional proximal or distal reabsorption as related to glomerular filtration rates or renal plasma flow were equally distributed between normal and renal subjects, except in the presence of a severe renal function impairment, where both variables decreased exponentially. This suggests that in renal failure, sodium balance is maintained by a proportional decrease of proximal and distal sodium reabsorption in relation to glomerular filtration. Only in the presence of severe renal failure (GFR less than 30 ml/min) both variables are concomitantly readjusted to lower values.

Antihypertensive therapy with Ca2+. Antagonist verapamil and/or ACE inhibitor enalapril in NIDDM patients.

OBJECTIVE: To assess the efficacy and tolerance of a diuretic-free antihypertensive therapy with a Ca2+ antagonist and an angiotensin-converting enzyme (ACE) inhibitor in patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: After a 2-wk washout and a 4-wk placebo phase, 47 hypertensive patients with NIDDM randomly received verapamil or enalapril alone and, if blood pressure remained elevated, both agents combined over 30 wk. RESULTS: Verapamil or enalapril alone normalized blood pressure to less than 90 mmHg diastolic in 30 patients; verapamil decreased mean +/- SE blood pressure from 159/98 +/- 3/1 to 146/87 +/- 3/2 mmHg (n = 18, P less than 0.001) and enalapril from 166/99 +/- 5/2 to 146/86 +/- 3/1 mmHg (n = 12, P less than 0.001). In 17 patients who were still hypertensive after 10 wk of monotherapy, combination of both drugs decreased blood pressure from 170/104 +/- 4/2 to 152/90 +/- 4/2 mmHg (P less than 0.001). Fasting plasma glucose, glycosylated hemoglobin, serum fructosamine, total lipids, high-density and low-density lipoprotein cholesterol, apolipoproteins A-I and B, creatinine, and urinary albumin-creatinine ratio were not significantly modified. CONCLUSIONS: In hypertensive patients with NIDDM, a diuretic-free therapy based on the Ca2+ antagonist verapamil and/or the ACE inhibitor enalapril can effectively decrease blood pressure without adversely affecting carbohydrate and lipid metabolism.

Cardiovascular pressor reactivity after chronic converting enzyme inhibition.

In addition to inhibiting the formation of angiotensin II, chronic converting enzyme inhibition may affect other blood pressure modulating factors. The influence of an 8 week treatment phase with cilazapril on the activity of the renin-angiotensin-aldosterone and sympathetic nervous systems, the pressor reactivity to infused angiotensin II or norepinephrine, the chronotropic response to isoproterenol, and body sodium and plasma atrial natriuretic peptide concentrations was assessed in 11 normal subjects and 12 patients with essential hypertension. As compared to a 4 week placebo phase, cilazapril decreased arterial pressure in both study groups (from 124/83 +/- 9/6 to 114/77 +/- 9/5 mm Hg and from 143/102 +/- 13/7 to 137/96 +/- 10/10 mm Hg; P less than .025); exchangeable sodium (-158 mmol and, respectively, -104 mmol) and upright plasma aldosterone (-24% and -15%) also tended to fall. Heart rate, the chronotropic response to posture or isoproterenol, plasma norepinephrine levels, the concentration/pressor response curve to norepinephrine, plasma atrial natriuretic peptide concentration, plasma angiotensin II and the responses of blood pressure or plasma aldosterone to angiotensin II were unchanged after 8 weeks of cilazapril. Plasma renin activity increased (+175% to +650%). These findings indicate that the blood pressure lowering effect of cilazapril in the stable phase of pharmacological intervention is not associated with modifications of sympathetic-dependent pressor reactivity or beta-adrenergic sensitivity. Plasma angiotensin II concentration and angiotensin II-dependent pathways including the pressor and aldosterone responsiveness to angiotensin II are also unchanged.

Cardiovascular regulation during angiotensin converting enzyme inhibition with captopril in diabetes-associated hypertension.

Diabetes-associated hypertension is accompanied by high levels of body sodium and cardiovascular hyper-reactivity to noradrenaline. Captopril, a promising drug for the treatment of hypertension in diabetics, may influence sodium metabolism and adrenergic pathways. This possibility was investigated in 11 patients with non-azotaemic diabetes mellitus and hypertension, studied after a 3-week placebo phase and after an 8-week phase of captopril treatment (50-100 mg/day). Blood pressure, exchangeable body sodium, blood volume, plasma renin activity, angiotensin II (Ang II), aldosterone, catecholamine levels and the pressor reactivity to infused Ang II or noradrenaline were measured. Compared with placebo, captopril caused a significant decrease in arterial pressure and stimulation of plasma renin activity. Exchangeable sodium, blood volume, plasma Ang II, aldosterone, noradrenaline and adrenaline levels, the pressor and aldosterone responsiveness to infused Ang II and the pressor response to infused noradrenaline (alone or combined with atropine) were not modified. These findings suggest that in hypertensive diabetics angiotensin converting enzyme inhibition causes a marked decrease in blood pressure. The mechanism of action is unrelated to changes in body sodium or noradrenergic-dependent pressor reactivity. In the stable phase of therapy, Ang II-dependent pathways are left unaltered when captopril is administered twice a day.

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.

Body sodium in normal subjects predisposed to hypertension.

Exchangeable sodium is lower than normal in young male patients with essential hypertension. This may reflect a primary or secondary abnormality. To investigate this question, exchangeable body sodium was measured in 31 normotensive men with positive and 31 normotensive men with negative family history of essential hypertension on a normal sodium intake (150 mmol/day). Blood pressure (BP) tended to be higher in the former group (p less than 0.005) but age, urinary sodium excretion, plasma renin activity, and aldosterone levels or creatinine clearance were comparable. Exchangeable sodium averaged 100.8 +/- 7.1% in subjects with positive and 100.2 +/- 6% in those with negative family history. In both groups, exchangeable sodium was unrelated to arterial pressure. The response of exchangeable sodium to variations in dietary sodium intake was further investigated in 13 subjects with and 10 subjects without family history. The change from a low (17 mmol/day) to a high (270 mmol/day) sodium diet elevated exchangeable body sodium to a comparable extent, despite a greater increase in BP in subjects with positive family history. Sodium-dependent suppression of renin, angiotension II, aldosterone, and plasma catecholamines was comparable between the two groups. These findings suggest that body sodium is normal and adapts normally to variations in dietary sodium intake in normotensive subjects with familial predisposition to hypertension. Body sodium depletion in early hypertension appears to be a secondary rather than a primary event.

Therapeutic efficacy of the HMG-CoA-reductase inhibitor pravastatin in hyperlipoproteinaemia type II.

The efficacy and safety of the HMG-CoA-reductase inhibitor pravastatin was assessed in a double-blind, placebo controlled study. Thirty patients (51 y) with hyperlipoproteinaemia Type IIa (N = 22) or IIb (N = 8) received for 16 weeks either pravastatin 5 mg b.d. for 8 weeks followed by 10 mg b.d. for 8 weeks (Group I), or 10 mg b.d. for 8 weeks followed by 20 mg b.d. to 16 weeks (Group II), or placebo (Group III). In Groups I and II, mean serum total cholesterol was reduced by -26% and -22%, respectively; low-density lipoprotein (LDL)-cholesterol decreased by -28% and -27%, apolipoprotein B by -25% and -23%, and apolipoprotein E by -9% (NS) and -16%, respectively. Serum high-density lipoprotein (HDL)-cholesterol was increased by 11% in Group II, and so the total/HDL-cholesterol ratio fell by 33%. Apoprotein A1 and A2 were not significantly changed. No serious clinical and laboratory abnormalities were observed. The data suggest considerable therapeutic efficacy of pravastatin in the treatment of Type II hyperlipoproteinaemia.

Antihypertensive efficacy and well-being during monotherapy and combination therapy with ketanserin.

The effects of ketanserin on blood pressure and well-being were investigated in 188 patients, aged 41-82 years, with mild to moderate essential hypertension. At entry, 107 were untreated, 42 were taking the diuretic combination hydrochlorothiazide (50 mg/day) plus amiloride (5 mg/day) and another 39 were taking the beta-blocker atenolol (100 mg/day). A single-blind, 4-week placebo run-in period was followed by 12 weeks' oral ketanserin treatment at 20 or 40 mg twice a day. This regimen significantly reduced systolic and diastolic blood pressures in each group. Response rates were greater in patients aged over 60 years. Compared with placebo, sleep disturbances, daytime fatigue and overall weakness decreased during ketanserin treatment (P less than 0.05 for all), but the incidence of dry mouth and stuffy nose increased. In patients older than 60 years there was a greater reduction of complaints than in younger patients. Ketanserin proved effective and well tolerated, improving peripheral circulatory symptomatology, particularly in older patients and those with a good blood pressure response.

[Treatment of arterial hypertension in non-oliguric renal failure]. / Die Behandlung des arteriellen Hochdrucks bei der nicht-oligurischen Niereninsuffizienz.

In patients with chronic renal disease, hypertension represents an important risk factor for the development of cardiovascular complications. Moreover, it appears possible that the progression of chronic renal failure may be slowed by carefully adjusted antihypertensive therapy. Therefore, blood pressure needs to be monitored very closely in patients with kidney disease and, when indicated, antihypertensive treatment should be started as soon as blood pressure begins to rise. Antihypertensive treatment of patients with non-oliguric renal failure has usually been started with dietary salt restriction and diuretic monotherapy. Other drugs, such as beta-blockers, sympathicolytic and/or vasodilating agents have been added successively. The possibility of beginning antihypertensive therapy with alternative compounds (beta-blocker, calcium antagonists and converting enzyme inhibitors) in patients with non-oliguric renal failure is discussed.

Hypotensive and diuretic effects of atrial natriuretic factor in diabetic patients.

Plasma levels of atrial natriuretic factor (ANF), and the effects of intravenously infused ANF (99-126) on renal filtration and blood pressure, were studied during different sodium intakes in six patients with uncomplicated diabetes mellitus. The change from a low (25 mmol/day) to a high (241 mmol/day) sodium intake was associated with a 2.5 fold increase in circulating immunoreactive ANF. On both sodium diets, an infusion of synthetic ANF (99-126) given at two different rates caused a progressive decrease of arterial pressure. On a low but not on a high sodium intake arterial hypotension occurred in two patients. Moreover, on a high sodium intake, ANF did not significantly modify glomerular filtration rate, the effective renal plasma flow and the plasma concentrations of renin and aldosterone. It increased the fractional excretion of sodium by 72%. On a low sodium intake ANF caused a progressive fall of glomerular filtration rates and effective renal plasma flow. It increased the fractional excretion of sodium by 100%, and increased plasma renin and aldosterone levels. In patients with uncomplicated diabetes mellitus, circulating ANF responds physiologically to variations in sodium intake. A low sodium diet could predispose to arterial hypotension and renal functional impairment during infusion of ANF (99-126).

[Blood pressure lowering action and tolerance of ketanserin in mono- or combination therapy]. / Blutdrucksenkende Wirksamkeit und Verträglichkeit von Ketanserin in Mono- oder Kombinationstherapie.

The antihypertensive efficacy and tolerability of the 5HT2-receptor antagonist ketanserin was investigated in 188 patients aged 41 to 82 years with mild to moderate essential hypertension. Ketanserin was given as monotherapy (n = 107) as well as in combination with either the diuretic hydrochlorothiazide/amiloride (n = 42) or the betablocker atenolol (n = 39) for 12 weeks. Compared to placebo, ketanserin lowered systolic blood pressure by 11 +/- 16 (SD), 9 +/- 13 and 9 +/- 11 mm Hg (p less than 0.01 for all) and diastolic blood pressure by 9 +/- 10, 10 +/- 9 and 7 +/- 9 mm Hg (p less than 0.001 for all), in the three treatment groups; body weight, serum sodium, potassium, uric acid, cholesterol and triglycerides remained unchanged. The incidence of withdrawals due to unwanted effects was 4% on ketanserin monotherapy, and 12% and 10% on the diuretic/ketanserin and the betablocker/ketanserin combination respectively. Well-being during ketanserin therapy was improved in the older patients in particular; sleep disturbances, daytime fatigue and overall weakness decreased. Ketanserin was well tolerated in combination with the diuretic, whereas in combination with the betablocker the occurrence of dry mouth and stuffy nose was slightly higher. - Ketanserin proved to be an effective antihypertensive drug comparable to other blood pressure lowering agents. It can be combined advantageously with a potassium sparing diuretic or a betablocker. The greater efficacy and tolerability in patients greater than or equal to 60 years qualify ketanserin primarily as an antihypertensive agent for older patients.

Hypotension and renal impairment during infusion of atrial natriuretic factor in liver cirrhosis with ascites.

Plasma immunoreactive atrial natriuretic factor (irANF) levels and the effects of alpha-human ANF (alpha-hANF) infusion were investigated in 7 patients with liver cirrhosis and ascites. Under basal conditions, supine blood pressure (BP) averaged 136/76 +/- 9/4 mm Hg (mean +/- SEM). Plasma irANF concentrations (124 +/- 33 pg/ml) were higher (p less than 0.01) than those in age-matched normal subjects (47 +/- 5 pg/ml). Plasma renin activity (PRA 5.9 +/- 2.2 ng/ml/h), aldosterone (18 +/- 7 ng/dl) and norepinephrine (NE, 66 +/- 5 ng/dl) levels were also elevated compared to the age-related normal range. Alpha-hANF infusion for 60 min at 0.036 micrograms/kg/min decreased the mean BP (-14%; p less than 0.05), increased PRA (+179%; p less than 0.05) and plasma NE (+24%; p less than 0.05). Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), diuresis and natriuresis were not modified. A subsequent 60-min infusion of alpha-hANF at 0.067 micrograms/kg/min produced a marked fall in mean BP (-26%; p less than 0.001), hemoconcentration (hematocrit +6%; p less than 0.001) despite stable body fluid balance and a further increase in PRA (+350%, p less than 0.005). GFR and ERPF were severely reduced (-55 and -56%, respectively; p less than 0.001), while diuresis and natriuresis were not modified. Plasma aldosterone was unaltered during, but rose (+72%; p less than 0.01) after the cessation of alpha-hANF infusion. Variations in natriuresis during alpha-hANF infusion correlated positively with BP (r = 0.47; p less than 0.01), ERPF (r = 0.53; p less than 0.01) or GFR (r = 0.51; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Yohimbine and aldosterone responsiveness to angiotensin II or corticotrophin in normal subjects.

In normal man the sympathetic nervous system exerts an inhibitory influence on aldosterone responsiveness to angiotensin II. The possible role of alpha-2 adrenoceptors was assessed by studying the changes of plasma aldosterone during an angiotensin II infusion at the dose of 1, 2, 5 and 10 ng/kg. min or after corticotrophin infusion, 0.25 mg, in 8 normal subjects before and after treatment with the selective alpha-2 adrenoceptor antagonist, yohimbine, at a maximal dosage of 60 mg daily. Yohimbine did not modify blood pressure, body weight, the supine levels of angiotensin II, renin and aldosterone, the pressor response to angiotensin II and the correlation relating plasma aldosterone to plasma angiotensin II obtained during infusion studies. These findings suggest that the inhibitory influence of the sympathetic nervous system on aldosterone responsiveness to angiotensin II.