Differential brain atrial natriuretic peptide expression co-segregates with occurrence of early stroke in the stroke-prone phenotype of the spontaneously hypertensive rat

OBJECTIVE: To determine how the downregulation of atrial natriuretic peptide (ANP) gene expression, previously demonstrated to occur only in the brain of the stroke-prone spontaneously hypertensive rat (SHRsp), in contrast to the stroke-resistant SHR (SHRsr), co-segregates with stroke occurrence in SHRsp/SHRsr F2 descendants in order to study the 'protective' role towards stroke previously demonstrated in SHRsp for the quantitative trait locus STR2 that also carries the ANP gene. DESIGN AND METHODS: Eight male SHRsp, eight male SHRsr and 16 male SHRsp/SHRsr F2-intercross animals (progeny of brother/sister mated F1 hybrids from an original cross between F0 SHRsp and SHRsr) were selected for this study. All rats were exposed to a stroke-permissive Japanese-style diet starting at the age of 6 weeks. Half of the F2 animals had early strokes; the remainder had late strokes. Blood pressure was measured before sacrifice. Analysis of brain ANP expression using an RNase protection assay was performed in all animals. RESULTS: Downregulation of brain ANP in the stroke-prone phenotype was found to co-segregate with the occurrence of early strokes in the F2 rats independently of blood pressure levels. CONCLUSIONS: The observed lower expression of ANP in the brains of stroke-prone rats appears to be the result of an inhibitory effect by another gene or genes. It seems unlikely that this specific trait represents a primary protective mechanism.