Antagonism of vasopressin V1a and V1b receptors in the paraventricular nucleus decreases blood pressure and saline intake but not renal sympathetic nerve activity in DOCA-salt sensitive hypertension

Salt sensitivity is a primary risk factors for hypertension (HTN) which is one of the most persistent modifiable risk factors for cardiovascular disease. Furthermore, key mechanisms in salt-sensitive HTN (SS-HTN) etiology remain unclear. Modification of salt-appetite through neuromodulation has been proposed as a novel mechanism. The paraventricular nucleus of the hypothalamus (PVN) is a major center for neurohumoral control in blood pressure (BP) regulation, as is vasopressin (AVP) activity within the PVN. The role of AVP receptor (V1a and V1b) signaling at the PVN remains unknown in the progression of SS-HTN. In the DOCA rats, it has been shown that AVP is increased in the cerebrospinal fluid and plasma, and that V1a and V1b receptors are overexpressed in the diencephalon and may be important for salt appetite. However, the role of AVP signaling in DOCA-salt HTN has not been directly demonstrated. We hypothesized that V1a and V1b receptors are required for the elevated BP, saline consumption and elevated sympathetic tone in the DOCA-salt rats. We generated male and female DOCA-salt rats by implanting the DOCA pellet (100mg) in uninephrectomized Sprague Dawley rats (n = 4-6 per group) while the DOCA vehicle group received the pellet with no deoxycorticosterone acetate. At the time of DOCA implantation siRNA oligonucleotides against V1a and V1b receptors (siV1) or scrambled siRNA (siScr) were microinjected stereotaxically bilaterally into the PVN. One week later (DOCA day 7, D7), Kaha dual BP and SNA telemeters were implanted to measure BP and renal sympathetic nerve activity (RSNA) in conscious freely moving rats for 10 days continuously. Saline intake was recorded daily. Data are expressed as mean +/- standard error and were analyzed by mixed effects ANOVA or t-test, where appropriate. BP and saline consumption at D14 of DOCA treatment were significantly reduced in siV1 DOCA-salt rats compared to the siScr counterparts, (24 hr mean arterial pressure: 104 +/- 5 vs. 155 +/- 2 mmHg, p < 0.001; saline intake: 114.3 +/-15.8 vs. 243.9 +/- 29.5 ml/24 hours). However, no effect on renal sympathetic burst incidence was observed between siV1 and siScr DOCA-salt rats throughout the study (i.e. 2.61 +/- 0.30 vs. 1.84 +/- 0.15 bursts/beat at D14). Likewise, no differences in width 50 were observed between D7, D10 and D14, respectively in siScr (17.38 ± 1.78, 19.32 ± 2.90, 18.44 ± 0.30 ms) and siV1 DOCA rats (21.77 ± 0.99, 19.14 ± 1.58, 18.38 ± 1.26 ms ) and Tau (9.98 ± 0.63, 8.36 ± 1.25, 8.14 ± 0.19 ms vs. 9.75 ±2.02, 8.17 ± 0.57, 7.63 ± 0.46 ms), while the bursts were actually taller for D7, D10 and D14 in siV1 DOCA (9.32 ± 4.82, 7.56 ± 4.44, 7.09 ± 4.34 microV ), compared to siScr DOCA (1.42 ± 0.30, 2.43 ± 0.02, 3.47 ± 0.82 microV, p < 0.001). These results partially supported our hypothesis, where siRNA knockdown of V1a/V1b receptors in the PVN abate the hypertension in the DOCA-salt rat model. This effect was paired with a suppression of the saline intake. Counter to our hypothesis, these data showed RSNA incidence remained unaffected while burst height actually increased in V1a/V1b knockdown DOCA-salt rats. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.