NERVE GROWTH-FACTOR GENE AND HYPERTENSION IN SPONTANEOUSLY HYPERTENSIVE RATS

Objective High blood pressure in spontaneously hypertensive rat (SHR) is associated with increased sympathetic innervation of key tissues, p ossibly as the result of increased nerve growth factor (NGF). The aim of this study was to test for genetic linkage of the NGF gene to high blood pressure, Design We studied NGF gene expression in young SHR and examined linkage of the NGF locus to mean arterial pressure in geneti cally segregating crosses of SHR and normotensive Donryu (DRY) rats. M ethods NGF mRNA was measured by Northern blot, and a restriction fragm ent length polymorphism of the NGF gene revealed after digestion with the Nsil restriction enzyme was used to study inheritance. Results Lev els of NGF mRNA were detected easily in the kidneys of 2-, 4- and 10-w eek-old SHR but not in age-matched DRY rats. In an F-2 population, the blood pressure of rats homozygous for the DRY NGF allele was 6 mmHg l ess than in heterozygotes and 8 mmHg less than in rats homozygous for the SHR NGF allele (analysis of variance, P < 0.004). In backcross rat s the blood pressure of NGF heterozygotes was not significantly differ ent from that of SHR homozygotes. Conclusion These results indicate di fferences in renal NGF mRNA in SHR during the development of hypertens ion and suggest that a genetic locus in or near the NGF gene contribut es in a Mendelian dominant pattern to a significant increment in blood pressure in SHR.