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 S HRsp/SHRsr F-2 descendants in order to study the 'protective' role towards stroke previously demonstrated in SHRsp for the quantitative trait locus ST R2 that also carries the ANP gene. Design and methods Eight male SHRsp, eight male SHRsr and 16 male SHRsp/SHR sr F-2-intercross animals (progeny of brother/sister mated F-1 hybrids from an original cross between F-0 SHRsp and SHRsr) were selected for this stud y. All rats were exposed to a stroke-permissive Japanese-style diet startin g at the age of 6 weeks. Half of the F-2 animals had early strokes; the rem ainder had late strokes. Blood pressure was measured before sacrifice, Anal ysis 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 F-2 rats indep endently of blood pressure levels. Conclusions The observed lower expression of ANP in the brains of stroke-pr one rats appears to be the result of an inhibitory effect by another gene o r genes. It seems unlikely that this specific trait represents a primary pr otective mechanism. J Hypertens 1999, 17:1849-1852 (C) Lippincott Williams & Wilkins.