Increased blood pressure in adult offspring of families with Balkan Endemic Nephropathy: a prospective study

BACKGROUND: Previous studies have linked smaller kidney dimensions to increased blood pressure. However, patients with Balkan Endemic Nephropathy (BEN), whose kidneys shrink during the course of the disease, do not manifest increased blood pressure. The authors evaluated the relationship between kidney cortex width, kidney length, and blood pressure in the offspring of BEN patients and controls. METHODS: 102 offspring of BEN patients and 99 control offspring of non-BEN hospital patients in the Vratza District, Bulgaria, were enrolled in a prospective study and examined twice (2003/04 and 2004/05). Kidney dimensions were determined using ultrasound, blood pressure was measured, and medical information was collected. The parental disease of BEN was categorized into three groups: mother, father, or both parents. Repeated measurements were analyzed with mixed regression models. RESULTS: In all participants, a decrease in minimal kidney cortex width of 1 mm was related to an increase in systolic blood pressure of 1.4 mm Hg (p = 0.005). There was no association between kidney length and blood pressure. A maternal history of BEN was associated with an increase in systolic blood pressure of 6.7 mm Hg (p = 0.03); paternal BEN, +3.2 mm Hg (p = 0.35); or both parents affected, +9.9 mm Hg (p = 0.002). There was a similar relation of kidney cortex width and parental history of BEN with pulse pressure; however, no association with diastolic blood pressure was found. CONCLUSION: In BEN and control offspring, a smaller kidney cortex width predisposed to higher blood pressure. Unexpectedly, a maternal history of BEN was associated with average increased systolic blood pressure in offspring

Vasodilator effects of sodium nitroprusside, levcromakalim and their combination in isolated rat aorta

1. The endothelial modulation of the relaxant responses to the nitric oxide (NO) donor sodium nitroprusside (SNP) and the K(ATP) channel opener levcromakalim (LEM) and the interactions between these agents were analysed in isolated rat aorta. 2. LEM-induced relaxation was unchanged by endothelium removal or by the presence of L-NAME (10(−4) M) or ODQ (10(−6) M). In contrast, in KCl- (25 mM), but not in noradrenaline- (NA, 10(−6) M) contracted arteries, SNP-induced relaxation was augmented by endothelium removal but not by L-NAME, indomethacin, glibenclamide nor charybdotoxin plus apamin. 3. The isobolographic analysis of the interactions between exogenously activated K(ATP) channels and cyclic GMP using mixtures of SNP and LEM revealed that there were no interactions between both drugs at the proportions at which both drugs were active. However, the points for the SNP : LEM mixtures in proportions 10 : 1 and 1 : 10,000 (i.e. at concentrations at which LEM and SNP were inactive, respectively) fell significantly above the line of additivity indicating that there were negative interactions between both drugs at these selected proportions (about 5- and 2 fold inhibition, respectively). The former interaction was sensitive to glibenclamide, whereas the latter was insensitive ODQ. The magnitude of the 10 : 1 SNP : LEM interaction was smaller in endothelium-intact arteries and was absent in arteries stimulated by NA. 4. In conclusion, the relaxations induced by LEM and SNP were additive. However, the presence of endothelium and low concentrations of LEM inhibited SNP-induced relaxation. Both inhibitory effects were not additive and were only observed in KCl- and not in NA-contracted aortae