IMPAIRED VASORELAXANT RESPONSES TO NATRIURETIC PEPTIDES IN THE STROKE-PRONE PHENOTYPE OF SPONTANEOUSLY HYPERTENSIVE RATS

Background We have previously shown that a locus on rat chromosome 5, termed STR 2, co-localizes with the genes encoding atrial natriuretic and brain natriuretic peptides, and is closely linked to the developme nt of strokes in rats of a F-2 hybrid cohort obtained by crossing stro ke-prone spontaneously hypertensive rats and spontaneously hypertensiv e rats. We also demonstrated that there are significant differences in vascular functioning that are co-segregated with stroke latency of st roke-prone spontaneously hypertensive rats. Objective To investigate t he vascular responses to natriuretic peptides in the stroke-prone phen otype of spontaneously hypertensive rats. Design and methods In view o f the important vasoactive properties of natriuretic peptides, we test ed the vascular responses to 10(-11)-10(-9) mol/l atrial natriuretic p eptide and to 10(-11)-10(-7) mol/l brain natriuretic peptide in isolat ed rings of aortas and internal carotid arteries obtained from stroke- prone and stroke-resistant spontaneously hypertensive rats. The 6-week -old rats were exposed for 4 weeks either to their regular diet (n = 1 5 of both strains) or to the stroke-permissive Japanese-style diet (n = 14 of both strains). A group of 14 normotensive, age-matched and sex -matched Wistar-Kyoto rats was also studied. Results Systolic blood pr essures in stroke-prone and stroke-resistant spontaneously hypertensiv e rats were similar, and were significantly higher than those in Wista r-Kyoto rats. Vascular responses to nitroglycerin, atrial natriuretic peptide, and brain natriuretic peptide in rats of the two hypertensive strains and in Wistar-Kyoto rats fed their regular diet were comparab le. In contrast, the vasorelaxant responses to atrial natriuretic pept ide in stroke-prone spontaneously hypertensive rats fed Japanese diet were lower both in aortas and in internal carotid arteries than were t hose in spontaneously hypertensive rats (both P< 0.05 by analysis of v ariance) and in Wistar-Kyoto rats (both P< 0.05). Similarly, vasorelax ant responses to brain natriuretic peptide were lower both in aortas a nd in internal carotid arteries of stroke-prone spontaneously hyperten sive rats than they were in spontaneously hypertensive rats (both P< 0 .05) and in Wistar-Kyoto rats (P< 0.05). The responses to nitroglyceri n in the stroke-prone spontaneously hypertensive rats and spontaneousl y hypertensive rats fed Japanese-style diet were also similar. Conclus ion The vasorelaxant effects of natriuretic peptides are impaired ire stroke-prone spontaneously hypertensive rats. This abnormality could p lay a role in the pathogenesis of stroke incidence in this hypertensiv e model. (C) 1998 Rapid Science Ltd.