Effect of chromosome 19 transfer on blood pressure in the spontaneously hypertensive rat

Linkage studies in the spontaneously hypertensive rat (SHR) have suggested that a gene or genes regulating blood pressure may exist on rat chromosome 19 in the vicinity of the angiotensinogen gene. To test this hypothesis, we measured blood pressure in SHR progenitor and congenic strains that are ge netically identical except for a segment of chromosome 19 containing the an giotensinogen gene transferred from the normotensive Brown Norway (BN) stra in. Transfer of this segment of chromosome 19 from the BN strain onto the g enetic background of the SHR induced significant decreases in systolic and diastolic blood pressures in the recipient SHR chromosome 19 congenic strai n. To test for differences in angiotensinogen gene expression between the c ongenic and progenitor strains, we measured angiotensinogen mRNA levels in a variety of tissues, including aorta, brain, kidney, and liver. We found n o differences between the progenitor and congenic strains in the angiotensi nogen coding sequence or in angiotensinogen expression that would account f or the blood pressure differences between the strains. In addition, no sign ificant differences in plasma levels of angiotensinogen or plasma renin act ivity were detected between the 2 strains, Thus, transfer of a segment of c hromosome 19 containing angiotensinogen from the BN rat into the SHR induce s a decrease in blood pressure without inducing any major changes in plasma angiotensinogen levels or plasma renin activity. These results indicate th at the differential chromosome segment trapped in the SHR chromosome 19 con genic strain contains a quantitative trait locus that influences blood pres sure in the SHR but that this blood pressure effect is not explained by dif ferences in plasma angiotensinogen levels or angiotensinogen expression.