Genes encoding atrial and brain natriuretic peptides as candidates for sensitivity to brain ischemia in stroke-prone hypertensive rats

Previous studies suggested that atrial natriuretic peptide gene (Anp) and b rain natriuretic peptide gene (Bnp) are plausible candidate genes for susce ptibility to stroke and for sensitivity to brain ischemia in the stroke-pro ne spontaneously hypertensive rat (SHRSP). We performed structural and func tional analyses of these 2 genes in SHRSP from Glasgow colonies (SHRSPGla) and Wistar-Kyoto rats from Glasgow colonies (WKYGla) and developed a radiat ion hybrid map of the relevant region of rat chromosome 5. Sequencing of th e coding regions of the Anp and Bnp genes revealed no difference between th e 2 strains. Expression studies in brain tissue showed no differences at ba seline and at 24 hours after middle cerebral artery occlusion. Plasma conce ntrations of atrial natriuretic peptide (ANP) did not differ between the SH RSPGla and WKYGla, whereas concentrations of brain natriuretic peptide were significantly higher in the SHRSPGla as compared with the WKYGla (n=11 to 14; 163+/-21 pg/mL and 78+/-14 pg/mL; 95% confidence interval 31 to 138, P= 0.003). We did not detect any attenuation of endothelium-dependent relaxati ons to bradykinin or ANP in middle cerebral arteries from the SHRSPGla; ind eed the sensitivity to ANP was significantly increased in arteries harveste d from this strain (WKYGla: n=8; pD(2)=7.3+/-0.2 and SHRSPGla: n=8; pD(2)=8 .2+/-0.15; P<0.01). Moreover, radiation hybrid mapping and fluorescence in situ hybridization allowed us to map the Anf marker in the telomeric positi on of rat chromosome 5 in close proximity to D5Rat48, D5Rat47, D5Mgh15, and D5Mgh16. These results exclude Anp and Bnp as candidate genes for the sens itivity to brain ischemia and pave the way to further congenic and physical mapping strategies.