Key result
Male TG7371 transgene-positive rats exhibited significantly elevated plasma, kidney, heart, and lung ANG 1-7 concentrations and lower systolic blood pressure compared to control rats.
Why the study?
The study aimed to assess systemic circulatory and tissue activities of both the classical and alternative arms of the renin-angiotensin system in a new transgenic rat line expressing an ANG 1-7-producing fusion protein.
p-value: p=<0.05
The TG7371 transgenic rat model exhibits ubiquitous overexpression of ANG 1-7 without altering ANG II levels, resulting in lower blood pressure in males, providing a novel tool to study the protective arm of the renin-angiotensin system.
Hypothesis-generating for ANG 1-7 effects on BP in males; leaves open translation to human hypertension therapy.
The aim of the present study was to assess systemic circulatory and tissue activities of both the classical arm and of the alternative arm of the renin-angiotensin system (RAS) in a new transgenic rat line (TG7371) that expresses angiotensin-(1-7) (ANG 1-7)-producing fusion protein; the results were compared with the activities measured in control transgene-negative Hannover Sprague-Dawley (HanSD) rats. Plasma and tissue concentrations of angiotensin II (ANG II) and ANG 1-7, and kidney mRNA expressions of receptors responsible for biological actions of ANG II and ANG 1-7 [i.e. ANG II type 1 and type 2 (AT 1 and AT 2 ) and Mas receptors] were assessed in TG7371 transgene-positive and in HanSD rats. We found that male TG7371 transgene-positive rats exhibited significantly elevated plasma, kidney, heart and lung ANG 1-7 concentrations as compared with control male HanSD rats; by contrast, there was no significant difference in ANG II concentrations and no significant differences in mRNA expression of AT 1 , AT 2 and Mas receptors. In addition, we found that in male TG7371 transgene-positive rats blood pressure was lower than in male HanSD rats. These data indicate that the balance between the classical arm and the alternative arm of the RAS was in male TGR7371 transgene-positive rats markedly shifted in favor of the latter. In conclusion, TG7371 transgene-positive rats represent a new powerful tool to study the long-term role of the alternative arm of the RAS in the pathophysiology and potentially in the treatment of cardio-renal diseases.
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Červenka et al. (2024) studied Cardio-renal disease model (n=71). Ubiquitous expression of angiotensin-(1-7)-producing fusion protein (TG7371 transgenic rat) vs. Transgene-negative and Hannover Sprague-Dawley rats was evaluated on Plasma and tissue concentrations of ANG 1-7 and ANG II, and systolic blood pressure (p=<0.05). Male TG7371 transgene-positive rats exhibited significantly elevated plasma, kidney, heart, and lung ANG 1-7 concentrations and lower systolic blood pressure compared to control rats.
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