Abstract P237: Ileal Content Cross Transplantation Between Ovlt Lesioned (ovltx) And Sham Rats Alters The Hypertensive Response In The Doca Salt Model

Abstract

Limited studies suggest a relationship between gut microbiome changes and specific types of hypertension. Using the deoxycorticosterone acetate (DOCA) salt model in rats, our lab previously demonstrated that the hypertensive response in DOCA-treated rats requires an intact organum vasculosum of the lamina terminalis (OVLT), and that this nucleus is capable of mediating changes in the gut microbiome concomitant with increased blood pressure during DOCA-salt treatment. These changes were mitigated and offset by lesion of the OVLT, and bacterial populations in OVLT lesioned rats with attenuated hypertension resembled those in normal control rats. Therefore, our current hypothesis is that cross transplanted ileal content between OVLT lesion (OVLTx) and SHAM animals will decrease hypertension during DOCA salt treatment. Adult male Sprague-Dawley rats were randomly selected for OVLTx (n=3) or SHAM (n=3) operation. After 1 week of recovery, rats underwent uninephrectomy as well as implantation of telemetric blood pressure transducers and indwelling ileal catheters. After a 14-day recovery period, all rats were given a 2.0% NaCl diet and ad libitum 0.9% NaCl drinking solution. After 5 control days, each rat received a 100 mg SQ DOCA pellet implant. Exactly ten days after initiating DOCA treatment, rats underwent daily ileal content transplantation for 6 days. Approximately 2 ml of ileal content was withdrawn from the catheter in all rats and cross transplanted (between OVLTx and SHAM rats) on days 10-16 of DOCA treatment. Mean arterial pressure (MAP) was measured during 5 control days and 16 days of DOCA treatment. On days 3-6 and 9-10 of DOCA treatment, the chronic pressor response to DOCA was attenuated in OVLTx rats such that by day 10, MAP increased to 125±2 mmHg in SHAM rats compared to 112±3 mmHg in OVLTx rats. After 6 days of transplantation, MAP had decreased to 114±1 mmHg in SHAM rats, whereas MAP in OVLTx increased to 120±2 mmHg. Ileal content cross transplantation from OVLTx rats produced a strong reversal of the chronic hypertensive response to DOCA in SHAM rats, and therefore these results support a prominent role of an OVLT-sympathetic-gut microbiome axis in the development of hypertension.