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 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The angiotensin converting enzyme (ACE) inhibitors are a group of effective drugs with a unique mechanism of action. These drugs have proven to be useful for hypertension and congestive heart failure. Early clinical trials of captopril used doses that are now known to be inappropriately high, and dose-related adverse effects were observed frequently. The recognition that lower doses are effective has reduced the incidence of adverse reactions and resulted in improved patient tolerance. When patients are properly selected and correctable risk factors are removed, serious side effects are uncommon. Unfortunately, the early reputation of nephrotoxicity persists, as does the belief that significant blood dyscrasias, endocrine effects and rash are serious risks for the average patient. After wide use of captopril, enalapril and lisinopril, and investigational trials of nearly a dozen newer agents, a sufficiency of clinical observation, experimental evidence and accurate postmarketing recording of events is accumulating to allow insight into the major toxicities with regard to more intelligent patient selection, more rational dosing and proper identification of risk factors. The most common adverse reactions are cough and skin rash. It appears that the agents are generally not cross-reactive with regard to skin rash, although it is not clear whether this effect is drug-specific or class-specific with regard to cough. Statistically but not clinically significant lowering of haemoglobin and hematocrit is common; these effects are inconsequential in most patients. Neutropenia, once thought to be prevalent, now appears to be so only in patients with autoimmune or collagen-vascular disease; the majority of patients outside these groups are at low risk. Hyperkalaemia is a frequent occurrence. This should not be surprising in view of the effect of the ACE inhibitors on plasma aldosterone. When dietary potassium intake is regulated and sources of altered potassium excretion are identified, hyperkalaemia is seldom a serious problem. Identification of sodium and water deficits allows correction before the drugs are started, and the frequency of hypotension and hyperkalaemia caused by the drugs is quite low if these factors are properly managed. An unexpected finding emerging in recent years is the dry cough associated with ACE inhibitor therapy. Its mechanism is not definitely known. Nonsteroidal anti-inflammatory drugs may control this symptom in some patients. The frequent observation of proteinuria in patients taking ACE inhibitors has gained notice and sometimes caused undue alarm. It is difficult to separate disease effects in diabetes and hypertension from true drug effects.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Adverse effects of angiotensin converting enzyme (ACE) inhibitors. An update. 153 95

The role of renal alpha 2-adrenoceptors in the regulation of glomerular filtration and renal perfusion is unknown. We studied the effects of alpha 2-adrenergic blockade on renal hemodynamics in six patients with insulin-dependent diabetes mellitus (IDDM) and in six healthy subjects. At the basal state, glomerular filtration rate (GFR) was higher in IDDM although the difference from control levels was not statistically significant. Volume expansion, achieved by infusion of isotonic sodium chloride solution, during placebo infusion induced a significant drop in GFR in healthy subjects but not in IDDM patients. Infusion of the alpha 2-adrenoceptor antagonist idazoxan did not further modify the effect of volume expansion on GFR. Renal plasma and blood flow as well as filtration fraction were not significantly changed by volume expansion or idazoxan infusion. Plasma renin activity and plasma aldosterone levels decreased during volume expansion in both IDDM and control subjects. In conclusion, volume expansion induced decreased GFR in healthy controls but not in IDDM patients. Since infusion of idazoxan did not affect GFR or other parameters of renal hemodynamics, renal alpha 2-adrenoceptors do not seem to be involved in the regulation of renal function. Hence, enhanced renal alpha 2-adrenoceptor activity is not likely to underlie hyperfiltration as seen in IDDM.
Diabetes Res Clin Pract 1991 Dec
PMID:Effects of alpha 2-adrenergic blockade on renal hemodynamics in patients with insulin dependent diabetes mellitus. 168 5

It is well known that diabetes mellitus is often associated with hypertension. We previously reported the unresponsiveness of renin release to volume depletion with impaired renal prostaglandin E2 synthesis in rats with streptozotocin-induced diabetes. However, we have found that BioBreeding Worcester rats, spontaneously susceptible to diabetes mellitus either before or after the onset of diabetes, showed a pronounced fourfold to ninefold increase in plasma renin activity in comparison with control Wistar rats. Furthermore, these rats developed mild hypertension as high as 134 mm Hg after the age of 90 days. The hyperreninemia responded to 1-week sodium loading or restriction; the blood pressure increased during sodium loading. Oral administration of captopril (30 mg/kg) for 1 week resulted in a large blood pressure decrease (-47.1 +/- 5.9 mm Hg, n = 10) in comparison with controls (-17.0 +/- 4.7 mm Hg, n = 12). Vascular response to angiotensin II was also attenuated. Plasma angiotensin II levels were 5.7-fold higher and associated with a 1.5-fold increase of plasma aldosterone concentration compared with control rats, whereas angiotensinogen-plasma concentrations were lower than in control rats. The renal renin content determined enzymatically or histochemically was more enhanced in BioBreeding Worcester rats than in control rats, but the renal renin messenger RNA levels did not differ. These results suggest that the strain-specific hyperreninemia in BioBreeding Worcester rats might be due to posttranscriptional abnormalities of renal renin synthesis. Further work is needed to elucidate the specific mechanism or mechanisms responsible.
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PMID:Hyperreninemia due to increased renal renin synthesis in BioBreeding Worcester rats. 169 97

Glomerular hyperfiltration is a characteristic functional abnormality in insulin-dependent diabetes mellitus (IDDM) patients, but the underlying mechanisms remain controversial. Supine and ambulant plasma renin activity (PRA) and aldosterone were measured in ten IDDM patients with normal glomerular filtration rate (GFR), in ten IDDM patients with elevated GFR and in ten nondiabetic controls. Basal and stimulated PRA or aldosterone did not differ significantly between the three groups. These results suggest that in insulin-dependent diabetes the glomerular hyperfiltration is not causally related to hyperactivity of the renin-angiotensin-aldosterone system.
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PMID:Glomerular hyperfiltration in insulin-dependent diabetes mellitus: no evidence for enhanced activity of the renin-angiotensin-aldosterone system. 177 18

To investigate pathogenesis of arterial hypertension in diabetes mellitus, the authors measured parameters of central and peripheral hemodynamics, basal renin levels, angiotensin, aldosterone, kallikrein-kinin system. The results were analysed with regard to hypertension type: essential (EH), atherosclerotic (AH) and nephrogenic (NH). Hypokinetic circulation, defected vascular elasticity, activation of renin-angiotensin-aldosterone system and hypoactivity of kallikrein-kinin system were characteristic of EH and AH. Most pronounced changes in peripheral hemodynamics and hypoactivity of depressor kallikrein-kinin system were seen in NH.
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PMID:[Pathogenesis of arterial hypertension in diabetes mellitus]. 178 Jul 71

A 41-year-old man, complaining of leg cramps, was found to have persistent hyperkalemia. Except for mild hypertension, his physical examination and laboratory values to exclude connective tissue diseases and diabetes mellitus were normal. Renal function testing revealed a normal glomerular filtration rate and tubular capacity to acidify and dilute, as well as near-normal ability to concentrate his urine. Hormonal evaluation revealed a normal cortisol, as well as normal resting and stimulated renin and aldosterone levels. A selective defect in tubular potassium secretion was demonstrated. In the absence of aldosterone deficiency or renal dysfunction, it was assumed that the patient had primary renal resistance to aldosterone, known as pseudohypoaldosteronism. Treatment with hydrochlorothiazide controlled his hyperkalemia and hypertension. His case emphasizes the diagnostic and therapeutic factors that should be considered in evaluating and treating a non-hospitalized patient with sustained hyperkalemia.
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PMID:Pseudohypoaldosteronism: case report and discussion of the syndrome. 178 91

To investigate the influence of postural changes on plasma renin activity (PRA), plasma levels of human atrial natriuretic peptide (hANP) and on aldosterone in diabetes mellitus and autonomic neuropathy, ten patients with diabetes mellitus and autonomic neuropathy and ten patients with diabetes mellitus but without autonomic neuropathy were studied. Ten healthy subjects served as controls. Patients and controls were in supine position for 60 minutes, then changed posture sequentially to sitting (90 minutes) and to upright position (15 minutes). In controls, PRA was increased upon sitting and in the upright position, while hANP was decreased. Patients with autonomic neuropathy differed from controls in impaired renin stimulation, whereas in patients without autonomic neuropathy PRA responses to postural changes were only slightly decreased. In both groups of patients, the normal hANP responsiveness to postural changes was lacking. There were no differences in aldosterone levels between patients and controls. In patients with high basal hANP levels due to elevated systolic blood pressure renin responses to postural changes were decreased in comparison to those patients with low basal hANP levels. Thus, in patients with diabetes mellitus increased hANP levels which are not decreased in response to upright standing may contribute to the development of hyporeninism and its sequelae.
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PMID:[The influence of autonomic diabetic neuropathy and human atrial natriuretic peptide on adrenal gland function in postural changes]. 182 74

Eight male normoproteinuric Type I (insulin dependent) diabetic patients and eight age- and sex-matched non-diabetic control subjects were studied for their response to exercise. Systolic blood pressure showed an exaggerated response to exercise in the diabetic group (median 123, range 98-151 mmHg, pre-exercise vs. 187, 163-217 mmHg, immediately post exercise P less than 0.01) compared to the control group (median 112 (100-145) pre-exercise, 153 (138-178) post exercise). Resting noradrenaline levels were lower in the diabetic (D) compared with the control (C) group (D: 1.66, 0.55-3.92 nmol/l vs. C: 2.96, 2.04-4.49 nmol/l, P less than 0.02). Levels rose during exercise by 79% (25-307%) and 43% (4-90%) respectively (NS). Resting urinary sodium was raised in the diabetic group and fell during exercise (P less than 0.05) (D: 146, 74-244 mumol/min, C: 108.5 (83.4-151.0) pre-exercise vs. D: 73, 48-264 mumol/min, C: 81.7 (23.0-92.0) post exercise). Resting atrial natriuretic peptide levels were lower in the diabetic group (D: 10.1, 4.3-16.9 pmol/l vs. C: 16.0, 9.5-22.9 pmol/l, P less than 0.02) and levels rose significantly in both groups during exercise (D: 25.9, 5.2-38.9 pmol/l vs. C: 28.6, 17.3-47.2 pmol/l, P less than 0.05). We conclude that exercise provokes an exaggerated rise in systolic blood pressure and decrease in urinary sodium excretion in normoalbuminuric diabetic patients. These findings may reflect increased sensitivity to the renin-angiotensin-aldosterone system. Reduced atrial natriuretic peptide levels may stimulate sodium retention and increased blood pressure in early diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Abnormal blood pressure response to exercise in normoalbuminuric insulin dependent diabetic patients. 182 71

Subjects with Type 2 diabetes have been reported to have elevated total exchangeable sodium when compared with normal subjects. Sodium retention may contribute to the development of hypertension in these subjects. Atrial natriuretic factor may play a role in sodium and blood pressure homeostasis in Type 2 diabetes. We have studied plasma atrial natriuretic factor in 17 subjects with Type 2 diabetes (9M:8F; aged 49 +/- 2 years) (mean +/- SE) and in 17 age- (49 +/- 2 years) and sex-matched controls. Mean fasting blood sugar was 8.3 +/- 0.6 mmol l-1 in the diabetic subjects. After fasting from 2200h, subjects remained upright from 0745h until 0945h when blood was taken for plasma atrial natriuretic factor, plasma renin activity and serum aldosterone. Two litres of 0.15 mmol l-1 NaCl was infused intravenously between 1000h and 1400h while the subjects remained supine. Blood was taken hourly. At 0945h plasma atrial natriuretic factor was 3.8 +/- 0.4 pmol l-1 in diabetic subjects and 6.1 +/- 1.6 pmol l-1 in controls (NS), at 1000h after 15 mins supine 3.5 +/- 0.3 and 7.9 +/- 2.3 pmol l-1 respectively (p < 0.05) and increased to 9.4 +/- 1.5 and 9.4 +/- 1.2 pmol l-1 in diabetic subjects and controls at 1400h (NS; both p < 0.01 vs basal values). Serum aldosterone, plasma renin activity, blood pressure and urinary sodium output for 12h before, 4h during and 8h after the NaCl infusion were not different between groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res 1991 Nov
PMID:Basal and stimulated plasma atrial natriuretic factor in type 2 diabetes. 184 25

We present preliminary data of a study comparing captopril, a short acting, with lisinopril, a long acting ACE-inhibitor in 8 of 12 projected patients with severe chronic heart failure (NYHA III-IV) and one additional risk factor (e.g. diabetes mellitus, renal failure). The 8 patients were treated in a cross over design for 12 weeks with either drug. While lisinopril improved NYHA-class in all patients, captopril reached this goal in only 3. Renal function was stable in all patients. Captopril influenced hormones (renin, aldosterone, norepinephrine, epinephrine) and microalbuminuria less than lisinopril. The number of adverse reactions was smaller in lisinopril treated patients. These preliminary data demonstrate at least an equal efficacy of lisinopril compared to captopril in high risk patients with severe chronic heart failure.
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PMID:[Comparison of lisinopril and captopril in treatment of severe heart failure (NYHA III-IV) in high risk patients. Preliminary results of the trial]. 185 Sep 42


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