OVLT Lesion attenuates hypertension and polydipsia in 2‐kidney, 1‐clip hypertensive Rats

Abstract

Hypertension (HTN) is a multifaceted condition that affects one‐third of the population of western countries. It is well established that renal ischemia results in secondary renovascular HTN. Experimental renovascular HTN is induced in rats by creating stenosis of the left renal artery, thereby decreasing perfusion pressure (2K1C‐HTN), leading to increased renin‐angiotensin system activity which may act centrally to increase arterial pressure, sympathetic nerve activity, and thirst. The organum vasculosum of the lamina terminalis (OVLT) is a circumventricular organ which is responsive to blood borne substances such as angiotensin II and has been implicated in the regulation of arterial pressure, sympathetic activity, and thirst. Previous studies have shown that OVLT lesion attenuates development of the DOCA‐model of hypertension, but does not modify the water intake (Collister et al., 2018). In the present study we tested the hypothesis that the OVLT is required for the development of 2K1C‐HTN as polydipsia is observed in this model. Male Sprague‐Dawley rats (n=3‐5/group) were randomly selected to receive either electrolytic lesion of the OVLT (OVLTx) or sham operation. After one week, they were instrumented with telemeters to measure mean arterial pressure (MAP). Two weeks after OVLTx, the left renal artery was stenosed by application of a silver clip. MAP was measured continuously for 6 weeks and, once a week, rats were housed in metabolic cages for 24 hours to measure water intake and urine volume. At the end of the protocol, MAP was significantly (p<0.001) lower in OVLTx‐2K1C (134±8 mmHg) compared to sham lesion‐2K1C (163±6 mmHg) rats. In addition, water intake was significantly (p<0.001) lower in OVLTx‐2K1C (42±2 ml/day) compared to sham lesion‐2K1C (73±2 ml/day) rats. Similarly, urinary volume excretion was reduced in OVLTx‐2K1C (25±2 ml/day) compared to sham lesion‐2K1C (52±5 ml/day) rats. We conclude that the integrity of OVLT is required for the development of 2K1C hypertension as well the polydipsia observed following renal artery stenosis.