Impaired vasorelaxant responses to natriuretic peptides in the stroke-prone phenotype of spontaneously hypertensive rats

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 development of strokes in rats of a F2 hybrid cohort obtained by crossing stroke-prone spontaneously hypertensive rats and spontaneously hypertensive rats. We also demonstrated that there are significant differences in vascular functioning that are co-segregated with stroke latency of stroke-prone spontaneously hypertensive rats. OBJECTIVE: To investigate the vascular responses to natriuretic peptides in the stroke-prone phenotype of spontaneously hypertensive rats. DESIGN AND METHODS: In view of the important vasoactive properties of natriuretic peptides, we tested the vascular responses to 10(-11)-10(-9) mol/l atrial natriuretic peptide and to 10(-11)-10(-7) mol/l brain natriuretic peptide in isolated 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 = 15 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 pressures in stroke-prone and stroke-resistant spontaneously hypertensive rats were similar, and were significantly higher than those in Wistar-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 comparable. In contrast, the vasorelaxant responses to atrial natriuretic peptide in stroke-prone spontaneously hypertensive rats fed Japanese diet were lower both in aortas and in internal carotid arteries than were those in spontaneously hypertensive rats (both P < 0.05 by analysis of variance) and in Wistar-Kyoto rats (both P < 0.05). Similarly, vasorelaxant responses to brain natriuretic peptide were lower both in aortas and in internal carotid arteries of stroke-prone spontaneously hypertensive rats than they were in spontaneously hypertensive rats (both P < 0.05) and in Wistar-Kyoto rats (P < 0.05). The responses to nitroglycerin in the stroke-prone spontaneously hypertensive rats and spontaneously hypertensive rats fed Japanese-style diet were also similar. CONCLUSION: The vasorelaxant effects of natriuretic peptides are impaired in stroke-prone spontaneously hypertensive rats. This abnormality could play a role in the pathogenesis of stroke incidence in this hypertensive model.