ASSOCIATION AND COSEGREGATION OF STROKE WITH IMPAIRED ENDOTHELIUM-DEPENDENT VASORELAXATION IN STROKE-PRONE, SPONTANEOUSLY HYPERTENSIVE RATS

While hypertension is a major risk factor for stroke, it is not its so le determinant. Despite similar blood pressures, spontaneously hyperte nsive rats (SHR) do not share the predisposition to cerebrovascular di sease typical of stroke-prone spontaneously hypertensive rats (SHRSP). We investigated vascular function in male SHR and SHRSP as well as in SHRSP/SHR-F-2 hybrid animals. Animals were maintained on the appropri ate dietary regimen necessary for the manifestation of stroke. Among t he hybrid animals, a group of stroke-prone and a group of stroke-resis tant rats were selected. Blood pressure was similar in all groups. End othelium-independent vascular reactivity tested on isolated rings of t horacic aorta and basilar artery after death showed similar contractil e and dilatory responses to serotonin and nitroglycerin, respectively, in all groups. In contrast, endothelium-dependent relaxation, in resp onse to acetylcholine or substance P, was markedly reduced in SHRSP co mpared with SHR. Similarly, reduced vasodilatory responses were presen t in aortae of F-2 rats that had suffered a stroke when compared with SHR or F-2 rats resistant to stroke. The observed association and cose gregation of stroke with significant and specific impairment of endoth elium-dependent vasorelaxation among SHRSP and stroke-prone F-2 hybrid s, respectively, suggest a potential causal role of altered endotheliu m-dependent vascular relaxation in the pathogenesis of stroke.