Cross transplantation of ileal content from OVLT lesioned rats to SHAM rats attenuates DOCA‐salt hypertension

Abstract

Despite the growing interest in understanding the role of gut microbe-host interaction in the maintenance of health or disease states, a limited number of studies have been suggested relationship between gut microbiome changes and specific types of hypertension. The deoxycorticosterone acetate (DOCA)-salt model of hypertension in rats is known to have a neurogenic component linked to increased sympathetic nervous system activity. As such, our lab has recently shown the hypertensive response in DOCA-treated rats requires an intact organum vasculosum of the lamina terminalis (OVLT), a central hypothalamic circumventricular organ. Previously, we hypothesize the OVLT mediates changes in the gut microbiome associated with concomitant hypertension. Herein, we report the hypertensive effects of DOCA-salt treatment were significantly attenuated throughout the 24-hour day/night cycle in OLVT lesioned rats on days 1, 3, and 9-21 of DOCA treatment compared with sham rats. Increased blood pressure in DOCA-salt treated rats was accompanied by specific changes in regional gut microbial populations yet was mitigated and offset by lesion of the OVLT. 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 Approximately 2 ml of ileal content was withdrawn from the catheter in all rats and cross transplanted (between OVLTx and SHAM rats) on days 10-16 of DOCA treatment.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 16±2 mmHg in SHAM rats when compared to only 6±1 mmHg in OVLTx rats. After 6 days of cross-transplantation, MAP had decreased 11±1 mmHg in SHAM rats, whereas MAP in OVLTx increased 8±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.