Kidney renin mRNA levels in the early and chronic phases of two-kidney, one clip hypertension in the rat

The effect of clipping the left renal artery on left and right kidney renin mRNA levels during the early and chronic phases of two-kidney, one clip Goldblatt hypertension in the rat was studied. Renin mRNA levels were determined using northern and dot blotting. Four weeks after clipping, renin mRNA levels were sixfold higher in the left kidney and eightfold lower in the right kidney of the Goldblatt rats compared with the left kidney of the sham-operated rats. Similar analysis at 20 weeks after clipping showed a fourfold increase in the left kidney and a 16-fold suppression in the right kidney compared with age-matched sham-operated control rats. The study demonstrates the profound changes that occur in renin gene expression in the clipped and contralateral kidneys in this model of hypertension and shows that these changes persist into the chronic phase of the hypertension.     

A major structural abnormality in the renin gene of the spontaneously hypertensive rat

The renin genes of the spontaneously hypertensive rat (SHR) and Wistar-Kyoto (WKY) rat were compared by Southern blotting using cDNA and oligonucleotide probes. A 'deletion' of approximately 650 base pairs was found in the first intron (intron A) of the SHR gene compared with the WKY gene. Our studies strongly suggest that this is due to a decrease in the number of copies of the tandemly repeated sequence present within intron A of the rat renin gene. In both SHR and WKY, this region of the gene was found to be different from that of the parent Wistar rat and those of other Wistar-based inbred strains. The functional significance of the abnormality and any role it may have in hypertension in the SHR remain to be determined.     

Nutritional and socio-demographic risk indicators of malaria in children under five: a cross-sectional study in a Sudanese rural community

This paper reports the results of a cross-sectional study of the association between nutritional, environmental and socio-demographic factors, and malaria occurrence among 445 children under 5 years of age in a Sudanese rural community. The overall frequency of malaria as defined by a history of clinical illness during the previous 2 months was 27%. Malaria occurrence was positively associated with the degree of malnutrition as assessed by weight-for-age. The age-adjusted odds ratio for mild malnutrition and history of malaria was 1.2 (95% confidence interval (CI): 0.7-2.0) and for moderate malnutrition and malaria was 2.1 (95% CI: 1.1-4.0). Malaria was less frequent among children 0-11 months of age relative to older children (OR = 0.4; 95% CI:0.2-0.7), and was inversely associated with ownership of a refrigerator (OR = 0.5; 95% CI:0.36-0.94), an indicator of socio-economic status. Indicators of crowding were the best predictors of the risk of malaria. Less malaria was observed in households with three or more rooms (OR = 0.6; 95% CI:0.37-0.98) and more malaria was observed in households with more than five people (OR = 2.5; 95% CI:1.4-4.5). Malaria was slightly, but not significantly, more frequent among boys and was associated with anaemia, which was probably an outcome of malaria in the past. These data suggest that undernutrition may increase the risk of malaria, and draw attention to the importance of socio-economic and environmental factors in relation to this disease. These relationships deserve further examination in prospective follow-up studies that are better able to evaluate the temporal relations of malnutrition and malaria.     

Renal Mechanisms of Association between Fibroblast Growth Factor 1 and Blood Pressure

The fibroblast growth factor 1 (FGF1) gene is expressed primarily in the kidney and may contribute to hypertension. However, the biologic mechanisms underlying the association between FGF1 and BP regulation remain unknown. We report that the major allele of FGF1 single nucleotide polymorphism rs152524 was associated in a dose-dependent manner with systolic BP (P=9.65×10⁻⁵) and diastolic BP (P=7.61×10⁻³) in a meta-analysis of 14,364 individuals and with renal expression of FGF1 mRNA in 126 human kidneys (P=9.0×10⁻³). Next-generation RNA sequencing revealed that upregulated renal expression of FGF1 or of each of the three FGF1 mRNA isoforms individually was associated with higher BP. FGF1-stratified coexpression analysis in two separate collections of human kidneys identified 126 FGF1 partner mRNAs, of which 71 and 63 showed at least nominal association with systolic and diastolic BP, respectively. Of those mRNAs, seven mRNAs in five genes (MME, PTPRO, REN, SLC12A3, and WNK1) had strong prior annotation to BP or hypertension. MME, which encodes an enzyme that degrades circulating natriuretic peptides, showed the strongest differential coexpression with FGF1 between hypertensive and normotensive kidneys. Furthermore, higher level of renal FGF1 expression was associated with lower circulating levels of atrial and brain natriuretic peptides. These findings indicate that FGF1 expression in the kidney is at least under partial genetic control and that renal expression of several FGF1 partner genes involved in the natriuretic peptide catabolism pathway, renin-angiotensin cascade, and sodium handling network may explain the association between FGF1 and BP.