HYPERTENSION, CARDIAC-HYPERTROPHY, AND SUDDEN-DEATH IN MICE LACKING NATRIURETIC PEPTIDE RECEPTOR-A

Natriuretic peptides, produced in the heart, bind to the natriuretic p eptide receptor A (NPRA) and cause vasodilation and natriuresis import ant in the regulation of blood pressure, We here report that mice lack ing a functional Npr1 gene coding for NPRA have elevated blood pressur es and hearts exhibiting marked hypertrophy with interstitial fibrosis resembling that seen in human hypertensive heart disease, Echocardiog raphic evaluation of the mice demonstrated a compensated state of syst emic hypertension in which cardiac hypertrophy and dilatation are evid ent but with no reduction in ventricular performance, Nevertheless, su dden death, with morphologic evidence indicative in some animals of co ngestive heart failure and in others of aortic dissection, occurred in all 15 male mice lacking Npr1 before 6 months of age, and in one of 1 6 females in our study, Thus complete absence of NPRA causes hypertens ion in mice and leads to cardiac hypertrophy and, particularly in male s, lethal vascular events similar to those seen in untreated human hyp ertensive patients.