ANALYSIS OF PHENOTYPIC CONSEQUENCES OF RENIN GENE POLYMORPHISM IN LYON RATS

Objective To investigate phenotypic consequences of renin gene polymor phism between Lyon hypertensive (LH) and normotensive (LN) rats becaus e previously we demonstrated cosegregation of the LH allele with incre ased blood pressure in a cross of LH with LN rats. Design Two studies were conducted, Study 1 used a cohort of male F-2 rats from a LH x LN cross, Eighty-two rats homozygous for the hypertensive (HH) renin gene allele were compared with 82 rats homozygous for the normotensive (NN ) allele, Urinary steroid excretion was measured in 24 h urine samples collected from rats aged 6 weeks, The direct aortic blood pressure wa s recorded in 30-week-old rats and, after they had been killed, their kidney renin concentration (KRC) was measured. In study 2, renin, angi otensinogen and angiotensin converting enzyme plasma concentrations an d renin messenger RNA (mRNA) levels were measured in renal and extra-r enal tissues from 6- and 25-week-old LH and LN parental and HH and NN F-2 male rats, Methods Urinary steroids and plasma components of the r enin-angiotensin system (RAS) were measured using specific radioimmuno assays, mRNA levels were quantified by northern blotting, Results In s tudy 1, HH F-2 rats had a higher blood pressure (151.5 +/- 8.2 versus 146.0 +/- 7.4 mmHg, P < 0.001) and a lower KRC (514 +/- 203 versus 666 +/- 304 mu g A1/h per g cortex, P < 0.01) than did NN rats aged 30 we eks, In covariate analysis the decrease in KRC in HH rats was attribut able to their increased blood pressure rather than to the renin genoty pe. The renin genotype of rats aged 6 weeks was not associated with a change in the urinary excretion of aldosterone, desoxycorticosterone, corticosterone or 18-hydroxy desoxycorticosterone, in study 2, we foun d no difference either in plasma levels of RAS components or in renal or extrarenal renin mRNA levels either between parental LH and LN rats or between HH and NN F-2 rats apart from a higher plasma renin concen tration in LH rats aged 6 weeks. Renal, but not extra-renal, renin mRN A levels declined with age, Conclusions We found no evidence of a reni n genotype-dependent phenotypic difference in the RAS that could accou nt for the effect of the renin locus on blood pressure in Lyon rats, O ur findings suggest that the effect of the locus on blood pressure mig ht be due to an as yet unidentified gene linked to renin.