Renal angiotensin II type 1 receptor expression and associated hypertension in rats with minimal SHR nuclear genome

Autor: Julie Kretzer, Elaine W. Patterson, Anne K. Hart, Jeffrey L. Osborn, Jason A. Collett
Rok vydání: 2013
Předmět:
Zdroj: Physiological Reports
ISSN: 2051-817X
DOI: 10.1002/phy2.104
Popis: Angiotensin II (AII) has been linked as a causal factor in several experimental models of hypertension (HT) including Okamoto spontaneously hypertensive rats (SHR). The transmission and expression of AII type 1 receptors (AT1r) in SHR and the development of genetic HT remain unknown. It is hypothesized that tissue-specific expression of renin–angiotensin system (RAS) genes derived from SHR are linked to HT in offspring of SHR crossed with Brown Norway (BN) rats. Hypertensive female progeny of BN/SHR matings was backcrossed with founder BN males to generate the F1 and five backcross generations (BN/SHR-mt SHR ). Progeny were phenotyped according to normotension (NT: systolic arterial pressure [SAP] ≤ 124 mmHg), borderline hypertension (BHT: 124 ≤ SAP < 145 mmHg), and HT (SAP ≥ 145 mmHg). Six generations produced more HT (n = 88; 46%) than NT (n = 21; 11%) offspring. The mRNA expression of the RAS was evaluated in NT (n = 20) and HT (n = 20) BN/SHR-mt SHR across several generations. Quantitative realtime polymerase chain reaction analysis of kidney tissue showed increased expression of AII, type 1 receptors (Agtr1a )( ~2.5-fold) in HT versus NT rats, while other members of both the renal and systemic RAS pathway were not different. Western blot analysis from kidney homogenates showed that AT1r protein levels were higher (P < 0.05) in backcross generation 3 (BC3) HT versus NT rats. Evaluation of SAP as a function of AT1r expression by linear regression indicated positive correlation (P < 0.05) in kidney of BC3 BN/ SHR-mt SHR rats. Thus, elevated kidney AT1r expression may be involved in the development of HT in BN/SHR-mt SHR rats.
Databáze: OpenAIRE
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