Renin gene expression and cosegregation analysis in genetic hypertension.

To investigate the role of the renin gene in the pathogenesis of hypertension in the spontaneously hypertensive rat (SHR) of the Okamoto strain, we examined renin gene expression in various tissues in SHR at different stages of hypertension development (4, 12, 20 and 36 weeks of age, N=6-10) and we determined whether the renin allele of SHR cosegregates with high blood pressure. Measurements of kidney, adrenal gland and brainstem renin mRNA levels were made by a competitive reverse transcription - polymerase chain reaction method. Compared with age-matched normotensive Wistar Kyoto (WKY) rats, renin mRNA levels in the adrenal gland of SHR were higher at 4 and 12 weeks of age (p<0.05) prior to the development of adult hypertension. In the brainstem, renin mRNA levels were not different at 4 weeks of age but SHR levels were higher than WKY at 12 and 20 weeks of age (p<0.05). However, renal renin mRNA was consistently lower in SHR at all ages. In the cosegregation study, the correlation of blood pressure, bodyweight and the renin Bgl II restriction fragment length polymorphism (RFLP) was examined in 137 F2 rats derived from inbred SHR and WKY. Systolic blood pressure was measured by the tail-cuff method and mean arterial blood pressure was measured in conscious rats by cannulation of the carotid artery. The SHR renin allele cosegregated with higher blood pressure and bodyweight between 8 and 24 weeks of age in male F2 rats (n=66, p<0.05) and cosegregated with higher blood pressure between 12 and 24 weeks of age in female F2 rats (n=71, p<0.05). We conclude that the SHR renin gene contributes to hypertension development through increased expression in tissues involved in blood pressure regulation. Structural abnormalities in regulatory regions of SHR renin gene may provide a unifying explanation for our findings.