Ileal cross transplantion between OVLT lesioned and sham rats alters OVLT‐sympathetic‐gut microbiome axis function in DOCA‐salt hypertension.

Abstract

Recently, there has been growing interest in understanding the gut microbe‐host interaction in the maintenance of health or disease states, but relatively few studies have shown an association between the gut microbiome and specific types of hypertension. The deoxycorticosterone acetate (DOCA)‐salt hypertensive model in rats has a well described neurogenic component linked to increased sympathetic nervous system acitivity. As previously demonstrated by our laboratory, the hypertensive response in DOCA‐treated rats involves the organum vasculosum of the lamina terminalis (OVLT), a circumventricular organ that connects directly with the paraventricular nucleus (PVN) to increase sympathetic activity. In addition, it has been shown that celiac ganglionectomy supports a role of splanchnic innervation to the gut in the hypertensive response to DOCA. Indeed, we have previously shown that the OVLT plays a pivotal role in the development of DOCA‐salt hypertension. Moreover, we have also observed that this nucleus is able to mediate changes in the intestinal microbiome with the concomitant increase in blood pressure during DOCA salt hypertension. However, these changes were mitigated and offset by lesion of the OVLT and bacterial populations in OVLT lesioned rats with attenuated hypertension more closely resembled those in normal control rats. Therefore, we currently hypothesize that ileal transplantation from OVLT lesioned rats to SHAM operated rats will reverse or attenuate DOCA‐salt hypertension. Adult male Sprague‐Dawley rats were randomly selected for lesion of OVLT (OVLTx; n=3) or SHAM operation (OVLT SHAM; n=3), subsequently uninephrectomized and instrumented with telemetric blood pressure transducers as well as chronic indwelling ileal catheters. Rats were then subjected to DOCA‐salt for 16 days. 10 days after DOCA treatment, rats underwent daily ileal transplantation: approximately 2 ml of the ileal content was withdrawn from the ileal catheter in all rats and cross transplanted (between OVLTx and respective SHAM rats) on days 10–16 of DOCA treatment.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±1.8 mmhg in SHAM rats when compared to only 112±2.5 mmHg in OVLTx rats. After ileal cross transplantation, a progressive decrease in MAP in SHAM rats was observed. In fact, on the sixth day after transplantation, MAP was decreased to 114±1.2 mmHg in these animals, whereas in OVLTx rats MAP increased to 120±1.8 mmHg. Therefore, after ileal cross transplantation, a powerful reversal of the chronic hypertensive response was observed. Additionally, an opposite effect was observed in OVLTx rats in that blood pressure increased. These results support a prominent role of the OVLT‐sympathetic‐gut microbiome axis in the development of hypertension. As such, targeting these alterations in gut microbiota may have promising therapeutic potential to improve health and a role in the prevention and treatment of hypertension.Support or Funding InformationAmerican Heart Association Award: 19AIREA34380525