M. Azam et al., GENETIC-MAPPING OF SOLUBLE GUANYLYL CYCLASE GENES - IMPLICATIONS FOR LINKAGE TO BLOOD-PRESSURE IN THE DAHL RAT, Hypertension, 32(1), 1998, pp. 149-154
The nitric oxide (NO) signaling system, consisting of NO synthases, so
luble guanylyl cyclase, and cGMP, plays a prominent role in salt handl
ing and regulation of blood pressure. Soluble guanylyl cyclases are he
me-containing heterodimers (alpha/beta). The alpha 1/beta 1 isoform ha
s greater NO sensitivity than the alpha 1/beta 2. It has recently been
shown that expression of the beta subunits is altered in the kidney o
f the Dahl salt-sensitive rat, ie, the beta 1 subunit is decreased and
the beta 2 subunit increased. However, whether soluble guanylyl cycla
se is linked to salt sensitivity is not known. In the present study, w
e investigated linkage of guanylyl cyclase genes to blood pressure. al
pha 1 and beta 1 gene loci for soluble guanylyl cyclase were mapped to
rat chromosome 2, and the beta 2 gene locus was mapped to rat chromos
ome 5 using fluorescent in situ metaphase hybridization. By use of a r
at radiation hybrid panel, the gene loci were then further mapped with
respect to known quantitative trait locus markers of salt-sensitive h
ypertension in the Dahl rat on chromosomes 2 and 5, Genes for alpha 1
and beta 1 were closely Inked by two-point analysis to Na+,K+-ATPase a
lpha 1 isoform (LOD of 15.1 and 14.0, respectively) and calmodulin-dep
endent protein kinase II-delta loci (LOD of 14.3 and 12.9, respectivel
y), which have been previously shown to flank a quantitative trait loc
us for blood pressure in the Dahl rat. The alpha 1 and beta 1 genes we
re closely linked (LOD of 11.3; theta, 0.4). The beta 2 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 so
luble guanylyl cyclase subunit loci, ie, alpha 1, beta 1, and beta 2,
are good candidates for genes controlling salt-sensitive hypertension
in the Dahl rat.