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(Hypertension. 1999;33:290-297.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Genes Encoding Atrial and Brain Natriuretic Peptides as Candidates for Sensitivity to Brain Ischemia in Stroke-Prone Hypertensive Rats

M. Julia Brosnan; James S. Clark; Baxter Jeffs; Cervantes D. Negrin; Pascale Van Vooren; Silvia M. Arribas; Hilary Carswell; Timothy J. Aitman; Claude Szpirer; I. Mhairi Macrae; Anna F. Dominiczak

From the Department of Medicine and Therapeutics and Wellcome Surgical Institute, University of Glasgow (Scotland) (M.J.B., J.S.C., B.J., C.D.N., S.M.A., H.C., I.M.M., A.F.D.); Molecular Medicine Group, MRC Clinical Sciences Centre, London, England (T.Y.A.); and the Department of Molecular Biology, Universite Libre de Bruxelles (Belgium) (P.V.V., C.S.).

Correspondence to Prof Anna F. Dominiczak, Department of Medicine and Therapeutics, Western Infirmary, 44 Church St, Glasgow G11 6NT. E-mail anna.dominiczak{at}clinmed.gla.ac.uk

Abstract—Previous studies suggested that atrial natriuretic peptide gene (Anp) and brain natriuretic peptide gene (Bnp) are plausible candidate genes for susceptibility to stroke and for sensitivity to brain ischemia in the stroke-prone spontaneously hypertensive rat (SHRSP). We performed structural and functional analyses of these 2 genes in SHRSP from Glasgow colonies (SHRSP_Gla) and Wistar-Kyoto rats from Glasgow colonies (WKY_Gla) and developed a radiation hybrid map of the relevant region of rat chromosome 5. Sequencing of the coding regions of the Anp and Bnp genes revealed no difference between the 2 strains. Expression studies in brain tissue showed no differences at baseline and at 24 hours after middle cerebral artery occlusion. Plasma concentrations of atrial natriuretic peptide (ANP) did not differ between the SHRSP_Gla and WKY_Gla, whereas concentrations of brain natriuretic peptide were significantly higher in the SHRSP_Gla as compared with the WKY_Gla (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 relaxations to bradykinin or ANP in middle cerebral arteries from the SHRSP_Gla; indeed the sensitivity to ANP was significantly increased in arteries harvested from this strain (WKY_Gla: n=8; pD₂=7.3±0.2 and SHRSP_Gla: n=8; pD₂=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 position of rat chromosome 5 in close proximity to D5Rat48, D5Rat47, D5Mgh15, and D5Mgh16. These results exclude Anp and Bnp as candidate genes for the sensitivity to brain ischemia and pave the way to further congenic and physical mapping strategies.

Key Words: rats, inbred SHR • peptides • genes • genetics • hybridization

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