Effects of cilazapril and amlodipine on kidney function in hypertensive NIDDM patients.

Contrasting information has been reported concerning the course of renal function in NIDDM with hypertension alone or in association with renal damage. The aim of the present study was to elucidate the course of the glomerular filtration rate (GFR) in hypertensive NIDDM patients during antihypertensive therapy. Furthermore, we compared the effects of ACE inhibitors (cilazapril, Inibace, Roche, Milan, Italy) and Ca(2+)-channel blockers (amlodipine, Norvasc, Pfizer, Rome, Italy). Of the hypertensive NIDDM patients attending the outpatient's clinic of the internal medicine departments of the University of Padova and Sassari, 44 participated in the present study. Of these patients, 26 were normoalbuminuric and 18 microalbuminuric. They were randomly treated with either cilazapril or amlodipine. The target of antihypertensive treatment was a value < 140 mmHg for systolic and 85 mmHg for diastolic blood pressure (BP). Microalbuminuria was defined as an albumin excretion rate (AER) between 20 and 200 micrograms/min. GFR was measured by plasma clearance of 51Cr-labeled EDTA at baseline and every 6-12 months during a 3-year follow-up interval. A significant decrease was observed in the values of GFR, AER, and systolic and diastolic BP in normoalbuminuric and microalbuminuric patients during antihypertensive therapy. The GFR fall in the overall population of NIDDM patients was significantly and inversely related to the decrease of mean BP (diastolic + 1/3 pulse pressure) (r = -0.80, P < 0.0001) but not to that of HbA1c, triglycerides, and BMI. The GFR decline (mean +/- SE) per year in the normoalbuminuric patient was 2.03 +/- 0.66 ml.min-1 x 1.73 m-2 (95% CI 0.92-3.17) during cilazapril and 2.01 +/- 0.71 ml.min-1 x 1.73 m-2 (95% CI 0.82-3.11) during amlodipine therapy. The GFR decline per year in the microalbuminuric patient was 2.15 +/- 0.69 ml.min-1 x 1.73 m-2 (95% CI 0.86-3.89) during cilazapril and 2.33 +/- 0.83 ml.min-1 x 1.73 m-2 per year (95% CI 1.03-3.67) during amlodipine therapy. Cilazapril and amlodipine lowered AER to a similar extent in normoalbuminuric and microalbuminuric patients. No significant changes were observed concerning other clinical and biochemical features between the two antihypertensive therapies and particularly HbA1c, BMI, triglycerides, and cholesterol plasma values. These results support the tenet that arterial hypertension plays a pivotal role in contributing to renal damage in NIDDM, even when AER is normal. However, the degree of BP control, with both cilazapril and amlodipine, can successfully delay the slope of GFR decline in hypertensive NIDDM patients with or without incipient nephropathy.

Interaction of glucose and pyridostigmine on the secretion of growth hormone (GH) induced by GH-releasing hormone (GHRH).

In order to investigate the mechanisms by which hyperglycaemia induces an inhibition of GHRH-induced GH release, we gave the following treatments to seven normal men: a) GHRH 100 micrograms iv; b) pyridostigmine (PD) 120 mg po 60 min before GHRH; c) glucose 250 mg/kg iv as a bolus (10 min before GHRH) plus 10 mg/kg/min until the end of the test; d) glucose pyridostigmine and GHRH as above. Glucose significantly reduced GHRH-stimulated GH levels, whereas PD significantly enhanced them. When PD and glucose were given together, the effect on GHRH-stimulated GH secretion was not different from the algebraic sum of the single effects of the two substances. Thus glucose seems to be able to exert its inhibition, at least partially, also when pyridostigmine is coadministered.