Overexpression of regulator of G protein signaling 2 (RGS2) in the paraventricular nucleus reduces blood pressure in angiotensin II-induced hypertensive rats

Abstract

The hypothalamic paraventricular nucleus (PVN) is important in mediating sympathetic activity to regulate blood pressure. The regulator of G protein signaling 2 (RGS2) is a negative G protein regulator. RGS2 selectively regulates Gαq signaling, an important cause of hypertension and cardiac hypertrophy. However, little-to-no studies are being done related to G-protein-RGS2 signaling on the central mechanisms of blood pressure control and sympathetic activation. In this study, we hypothesized that central RGS2 overexpression changes blood pressure regulation by decreasing the response to angiotensin II (ANG II). We infused ANG II (200ng/kg/min) via an osmotic minipump to induce hypertension. These rats were outfitted with telemetry and measurements of blood pressure and heart rate over the next 14 days, with or without RGS2 adenovirus (AV) injection into the PVN. We found that days 3, 4, and 6 after virus transfection showed a significant difference between the group outfitted with only the ANG II pump versus those outfitted with both ANG II pumps and PVN AV injection. Results shown below are in order of ANG II pumps only, ANG II pump after AV, and ANG II pump + AV, respectively (unit in mmHg). Day 3: 155.5 +/- 9.4, 131.8 +/- 4.5, 134.3 +/-9.5, P<0.05; Day 4: 164.5 +/- 8.0, 140.3 +/- 7.0, 136.1 +/- 10.2, P<0.05; Day 6: 169.3 +/- 4.2, 144.4 +/- 4.5, 140.6 +/- 8.3, P<0.05. There was no significant difference between day 6 and the end of the experiment. Our real-time PCR and Western blot studies showed punched PVN tissue highly expressed RGS2 mRNA and protein. Further, in vitro study showed ANG II treatment affected RGS2 mRNA and protein expression in cultured hypothalamic neuronal cells. The findings suggest that RGS2 ameliorates ANG II-induced hypertension in rats, possibly via regulating central PVN-mediated blood pressure controlling and sympathetic activation. Funded by NIH R01-DK-114663 & R01-DK-129311 and USD G-RISE, NIH T32GM-136503. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.