LOCUS FOR THE INDUCIBLE, BUT NOT A CONSTITUTIVE, NITRIC-OXIDE SYNTHASE COSEGREGATES WITH BLOOD-PRESSURE IN THE DAHL SALT-SENSITIVE RAT

Alleles of the inducible nitric oxide synthase locus (Nos2) cosegregated highly significantly (P < 0.0001) with blood pressure in an F-2 population [F-2(S x MNS), n = 171] derived from a cross of inbred Dahl salt-sensitive (S) rats with Milan normotensive rats (MNS). In contrast, alleles at the constitutive brain nitric oxide synthase locus (Nos1) did not cosegregate with blood pressure in several F-2 populations. Nos2 was mapped on rat chromosome 10, Nine genetic markers, including the angiotensin-converting enzyme (Ace) and Nos2 loci spanning roughly 46 cM on rat chromosome 10, all cosegregated strongly with blood pressure in the F-2(S x MNS) Nos2 showed the highest LOD score of 6.3. Ace and Nos2 are 30 cM apart, In an F-2 population [F-2(S x WKY), n = 159] derived from a cross of S rats with Wistar-Kyoto (WKY) rats, Nos(2) alleles did (P = 0.0070), but Ace alleles did not (P = 0.91), cosegregate with blood pressure. We conclude that the Nos2 locus rather than the Nos1 locus is a candidate for influencing blood pressure in the S rat. There are probably two separate but linked quantitative trait loci (QTL) for blood pressure on rat chromosome 10, one marked by Ace and the other marked by Nos2, In F-2(S x MNS) functionally variant alleles at both QTL influence blood pressure, but in F-2(S x WKY) only the QTL marked by Nos2 is segregating alleles influencing blood pressure.