From the Department of Physiology, University of Melbourne, Parkville
(F.J.C., S.B.H.), and Bone Marrow Transplant Unit, Alfred Hospital, Prahran
(M.K.K.), Victoria, Australia.
Correspondence to Professor S.B. Harrap, Department of Physiology, University of Melbourne, Parkville, Victoria 3052, Australia. E-mail s.harrap{at}physiology.unimelb.edu.au
AbstractNerve growth factor
(NGF) controls the growth of sympathetic nerves and is increased in
young spontaneously hypertensive rats (SHR). The NGF gene has been
linked genetically with hypertension in the SHR strain and may explain
high NGF mRNA levels. To test for genetic linkage between the NGF gene
and its expression in vivo, we examined renal NGF mRNA levels in male
SHR, control Donryu rats (DRY), and F2 rats derived from
SHR and DRY at ages 2, 4, 10, and 20 weeks. Tail-cuff blood pressure
was measured at 4, 10, and 20 weeks of age. NGF mRNA levels in SHR (NGF
genotype: SS) were higher than those in DRY (NGF
genotype: DD) at 2, 4, and 10 weeks of age
(P<0.0001) but the same at 20 weeks of age. In the
F2 generation, the S allele was
associated with significantly (P=0.01) higher renal NGF
mRNA levels at 2 weeks of age. Mean NGF mRNA levels fell
(P=0.01) with age in F2 rats, and the
difference between SS and DD
genotype F2 rats diminished at older ages and was
not significant. In F2 rats there was a positive
correlation between the number of NGF S alleles
inherited and tail-cuff pressure (P<0.007). Our
findings indicate that the NGF locus is an important regulator of NGF
mRNA levels. It is likely that mutations in or near the NGF gene
explain in part high early NGF gene expression in SHR.
© 1998 American Heart Association, Inc.
Scientific Contributions
Nerve Growth Factor Gene Locus Explains Elevated Renal Nerve Growth Factor mRNA in Young Spontaneously Hypertensive Rats
Key Words: growth substances hypertension rats, inbred SHR gene expression kidney
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