From the Department of Internal Medicine (M.A., G.G., W.C., R.S.D.) and
Departments of Genetics and Development and Pediatrics (S.W., D.W.), Columbia
University, New York, NY. Dr Azam is currently at ExpressGen Inc, Chicago,
Ill.
Correspondence to Robert S. Danziger, MD, PH10–408, College of Physicians and Surgeons of Columbia University, 630 W 168th St, New York, NY 10032. E-mail rsd6{at}columbia.edu
Abstract—The nitric oxide (NO)
signaling system, consisting of NO synthases, soluble guanylyl cyclase,
and cGMP, plays a prominent role in salt handling and regulation of
blood pressure. Soluble guanylyl cyclases are heme-containing
heterodimers (
© 1998 American Heart Association, Inc.
Scientific Contributions
Genetic Mapping of Soluble Guanylyl Cyclase Genes
Implications for Linkage to Blood Pressure in the Dahl Rat
/ß). The 1/ß1 isoform has greater NO
sensitivity than the 1/ß2. It has recently been shown that
expression of the ß subunits is altered in the kidney of the Dahl
salt-sensitive rat, ie, the ß1 subunit is decreased and the ß2
subunit increased. However, whether soluble guanylyl cyclase is linked
to salt sensitivity is not known. In the present study, we
investigated linkage of guanylyl cyclase genes to blood pressure. 1
and ß1 gene loci for soluble guanylyl cyclase were mapped to rat
chromosome 2, and the ß2 gene locus was mapped to rat chromosome 5
using fluorescent in situ metaphase hybridization. By use of a
rat radiation hybrid panel, the gene loci were then further mapped with
respect to known quantitative trait locus markers of salt-sensitive
hypertension in the Dahl rat on chromosomes 2 and 5. Genes for 1 and
ß1 were closely linked by two-point analysis to
Na+,K+-ATPase 1 isoform (LOD of 15.1 and
14.0, respectively) and calmodulin-dependent protein kinase
II-
loci (LOD of 14.3 and 12.9, respectively), which have been
previously shown to flank a quantitative trait locus for blood pressure
in the Dahl rat. The 1 and ß1 genes were closely linked (LOD of
11.3; 
, 0.4). The ß2 gene locus was closely linked to the
endothelin-2 (ET-2) locus (LOD of 13.0), which has been shown to
cosegregate with blood pressure. We conclude that soluble guanylyl
cyclase subunit loci, ie, 1, ß1, and ß2, are good candidates for
genes controlling salt-sensitive hypertension in the Dahl rat.
Key Words: guanylyl cyclase • cyclic GMP • genetics • hypertension, salt-sensitive
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