These findings are compatible with a major role of one or more of renin, vasopressin, and noradrenaline in the pathophysiology of the fluid retention of heart failure; the manifestations are not counteracted by the rise in atrial natriuretic factor.

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The influence of cardiac innervation on the renal response to volume expansion was investigated. Systemic hemodynamic, plasma hormone, and renal clearance measurements were made before, during, and after intravenous administration of 1,000 ml 0.9% saline over 10 min to six control and six cardiac-denervated, chloralose-anesthetized mongrel dogs. Volume expansion resulted in a two- to threefold rise in plasma atrial natriuretic peptide (ANP) concentrations and a 50% rise in glomerular filtration rate (GFR) in both groups. Plasma renin activity (PRA) and plasma arginine vasopressin remained higher throughout in cardiac-denervated compared with control dogs. The marked increases in urine flow rate and sodium and free water clearances seen in the controls were attenuated or abolished after cardiac denervation. These differences were due to the influence of higher PRA and vasopressin in these animals compared with the controls, rather than differences in hemodynamic responses operating via GFR or in direct humoral responses via ANP secretion.

Objective-To determine the influence of insulin dependent diabetes on the prevalence of myocardial ischaemia and on global left ventricular systolic performance. Design-Stress treadmill electrocardiograms and simultaneous Doppler measurement of aortic maximum acceleration were obtained during exercise on symptom free subjects. The electrocardiograms were scored blindly according to the Minnesota code. Participants-39 identical twin pairs (22 male) discordant for insulin dependent diabetes and 39 non-diabetic controls of similar age and sex were examined. The twins and controls had a mean age of 37 (range 25-69) with a mean (SD) duration of diabetes in the diabetic twin of 17 (7) years. Those selected were normotensive and had no renal impairment. Results-Systolic blood pressure was significantly higher in the diabetic twins than in their non-diabetic cotwins both at rest (p < 0.05) and at peak exercise (p < 0.01). Electrocardiographic evidence of ischaemia was not correlated within twin pairs and was found in similar numbers of diabetic twins, their non-diabetic cotwins, and control subjects. Abnormal electrocardiograms were found in a similar number of diabetic twins (23%), non-diabetic cotwins (18%), and controls (15%). There was a significant correlation in Doppler measurements of global left ventricular systolic function within the identical twins; no significant difference was found for these Doppler measurements in the diabetic twins, non-diabetic cotwins, or controls. Conclusion-Exercise characteristics and cardiac function seem to be subject to shared genetic or shared environmental influences or both, whereas electrocardiographic features of ischaemia seem to be environmentally determined. In a selected cohort of diabetic identical twins without evidence of nephropathy there was no evidence that diabetes influenced the prevalence of myocardial ischaemia or global left ventricular systolic function. (Br Heart J 1994;71:341-348) Premature coronary artery disease is an important cause of morbidity and mortality in juvenile onset insulin dependent diabetes mellitus.'-2 The excess mortality from coronary artery disease is predominantly attributed to diabetic patients with persistent proteinuria, a hallmark of diabetic nephropathy.3 A less striking but considerably increased risk of coronary artery disease has also been reported in insulin dependent diabetes even in the absence of diabetic nephropathy.34 This effect could be due either to an influence of diabetes on risk factors for coronary artery disease or to an unrecognised genetic susceptibility to coronary disease. Risk factors for coronary artery disease are, however, only minimally altered by insulin dependent diabetes when renal function is normal and if diabetic control is good.56 To examine the effect of insulin dependent diabetes on the prevalence of myocardial ischaemia, in the absence of diabetic nephropathy, we have studied genetically identical twins discordant for diabetes. Myocardial ischaemia was estimated with exercise electroca...

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