Homocystein and carotid atherosclerosis in chronic renal failure.

BACKGROUND: Since total homocysteine (Hcy) is markedly elevated in patients with chronic renal failure (CRF), it has been presented as potential factor contributing to the high risk of cardiovascular disease (CVD) in CRF. The aim of the study was to examine the significance of elevated Hcy and other cardiovascular risk factors for carotid atherosclerosis in patients with CRF. MATERIAL AND METHODS: Fifty six patients 16-M, 40-F, average age 58+/-14.55, creatinine clearance 39.19+/-10.11 ml/min were examined. In addition, 20 control healthy subjects were examined. The association of Hcy levels and classic risk factors for atherosclerosis with common carotid intima-media thickness (IMT) was examined. B-mode ultrasound measurement of carotid IMT was performed in 56 hypertensive pts with CRF (glomerular filtration rate>20 ml/min and <90 ml/min), 44 hypertensive pts with normal renal function and 20 healthy volunteers. The mean duration of hypertension was 145.12 years. RESULTS: IMT in all examined hypertensive pts was increased above normal clinical value and significantly higher then in healthy controls (0.75+/-0.006/0.60+/-0.1, p<0.001). The carotid IMT was similar between hypertensive pts with CRF and hypertensive pts with normal renal function (0.74+/-0.1/0.76 +/-0.1, p>0.05). Significant predictors for IMT were age (r=0.358, p<0.04), duration of hypertension (r=0.395, p=0.023), diabetes duration (r=0.343, p<0.02), as well as duration of CRF (r=0.324, p<0.006). There was a negative correlation between IMT and glomerular filtration rate assessed by creatinine clearance (r=-0.303, p<0.003). Renal function, described by creatinine clearance was the strongest determinant for Hcy levels (r=-0.332, p<0.008). Increased IMT was estimated in pts with CRF compared to healthy controls (0.74+/-0.10 vs 0.59+/-0.10, p<0.001). We found association between Hcy and carotid IMT ( r=0.344, p<0.015). No consistent association was found between IMT and other specific for CRF cardiovascular risk factors. CONCLUSION: The study suggests that patients with mild renal failure have increased IMT of the common carotid artery and that elevated plasma Hcy level in CRF is associated with carotid intima- media thickening.

Interrelation between the renal sympathetic nerve and atrial natriuretic peptide in conscious long Evans rats subjected to sodium restriction.

The renal excretory function and plasma renin activity (PRA) were studied in conscious rats on a low sodium diet (25 mmol/kg) after atrial natriuretic peptide (ANP) infusion (100 ng/kg b.w./min) for 80 min through a catheter implanted in the right atrium. The half of the animals were with bilateral kidney denervation. The rats were housed every day from 8 a.m. to 2 p.m. in individual metabolic cages for urine collection and Na, Cl, osmolality and endogenous creatinine determination. At the last day of the experiments after the ANP infusion, blood was taken from the heart for electrolytes, endogenous creatinine and PRA. The effect of denervation was monitored by measuring of noradrenaline in kidney homogenate. The data indicated that even at low sodium diet ANP stimulates the diuresis and sodium excretion without changing the glomerular filtration rate (GFR). The kidney denervation combined with ANP infusion increased twice the diuresis and four times sodium excretion vs. the control animals. In the same time PRA was decreased by about 70%. We assume that the low sodium diet attenuates the effect of ANP in respect to the excretory function. This inhibitory effect is amplified by the renal sympathetic nerves. The decrease of PRA and possibly the increased activity of renal receptors after the denervation could explain the data obtained.

Effect of calcium blocking agent verapamil on blood pressure, ventricular contractility, parathyroid hormone, calcium and phosphorus in plasma, catecholamines, corticosterone and plasma renin activity in spontaneously hypertensive rats.

In four-month-old spontaneously hypertensive rats (SHR) the effect of a calcium blocking agent verapamil on blood pressure, ventricular contractility indices, parathyroid hormone (PTH), plasma renin activity (PRA), plasma and adrenal corticosterone content and catecholamines in hypothalamus, myocardium and adrenal gland was evaluated. Calcium and phosphorus in plasma were also determined. Verapamil treatment resulted in a significant decrease in systolic and diastolic blood pressure and a reduction in maximum left ventricular pressure. Verapamil exerted a negative inotropic effect, evaluated by a decrease in dP/dt max and dP/dt neg. PRA was elevated, calcium tended to decrease, and no changes in PTH and phosphorus were found. The hypotensive effect of verapamil in SHR was accompanied by a decrease in plasma and adrenal corticosterone content, and a fall in catecholamine concentration in adrenal glands and myocardium.