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

Abstract

Angiotensin II (AII) has been linked to hypertension in Okamoto Spontaneously Hypertensive Rats (SHR). The transmission and tissue specific 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 rats. A rat colony was developed by breeding a female Okamoto‐Aoki SHR (MAP=160mmHg) with a BN male (MAP=91mmHg). Hypertensive F1 female progeny were backcrossed with the founder BN to generate 5 subsequent backcross generations. F1 and backcross generation 3 (BC3) tissue AT1r protein expression were evaluated. Progeny were grouped as normotensive (NT<105mmHg; F1 n=0, BC4 n=8), borderline hypertension (BHT 105 ≤ MAP < 122 mmHg; F1 n=18, BC4 n=21) and hypertensive (HT MAP ≥ 122 mmHg; F1 n=15, BC4 n=16). AT1r protein expression between HT and BHT F1 progeny were similar in kidney, hypothalamus or forebrain. HT BC3 rats had greater kidney and hypothalamic AT1r expression but not FB compared to NT rats. There was a positive correlation between MAP and AT1r expression in kidney and hypothalami. These results demonstrate that tissue specific elevated AT1r expression may contribute to spontaneous hypertension in SHR/BN rats with minimal SHR genome inheritance.