Tissue Angiotensin II Type 1 Receptor Expression in Development of Hypertension in SHR/Brown Norway Congenic Rats

Abstract

Angiotensin II (AII) has been linked to hypertension in Okamoto Spontaneously Hypertensive Rats (SHR). The transmission and progeny expression of AII Type 1 receptors (AT1r) in SHR and the development of genetic hypertension remains unknown. It is hypothesized that tissue AT1r expression of genes derived from SHR are linked to elevated blood pressure in offspring of SHR crossed with normotensive, Brown Norway (BN) rats. Hypertensive female F1 progeny of SHR/BN matings were backcrossed with the founder BN male to generate F2 progeny. Arterial pressures (MAP) were measured by tail cuff plethysmography and offspring were sacrificed at 15–20 weeks of age for analysis of tissue AT1r. MAP of parent SHR was 151 mmHg and BN was 94 mmHg. Progeny were grouped according to normotension (NT<105mmHg; F1 n=0, F2 n=2), borderline hypertension (BHT 105 ≤ MAP < 122 mmHg; F1 n=18, F2 n=13) and hypertension (HT MAP ≥ 122 mmHg; F1 n=15, F2 n=13). AT1r expression in forebrain (0.918 ± 0.176), kidney (0.905 ± 0.050), and hypothalamus (1.28 ± 0.252) tissues in the F1 progeny of BHT and HT were similar (western blot analysis). These data suggest that tissue AT1r expression of genes transmitted to offspring from SHR females are correlated to elevated progeny blood pressure. Tissues of F3‐F6 SHR/BN congenic progeny will be analyzed to further evaluate the interactions of tissue AT1r expression and the genetic transmission of hypertension by female SHR.