The organum vasculosum of the lamina terminalis contributes to neurohumoral mechanisms of renal vascular hypertension

The organum vasculosum of the lamina terminalis (OVLT) is a forebrain circumventricular organ that modulates central autonomic control of arterial pressure and body fluid homeostasis. It has been implicated in the pathogenesis of rat models of hypertension that are driven by increased salt intake since OVLT lesion (OVLTx) attenuates both the DOCA-salt and angiotensin II-salt models. However, its contribution to the development of hypertension that is not salt-dependent, such as the 2 kidney, 1 clip (2K1C) renovascular model, is not clear. We recently reported that afferent renal denervation (ARDN) attenuates the pathogenesis of 2K1C hypertension in the rat and this was associated with a reduction of neurogenic pressor activity, water intake, vasopressin release, and renal inflammation, suggesting that afferent renal nerves, similar to OVLT, modulates central autonomic pathways that control arterial pressure and body fluid homeostasis. This idea led to the present study, which was designed to measure the effect of OVLTx on arterial pressure and body fluid homeostasis in 2K1C-HTN rats. Male Sprague-Dawley rats were randomly selected to receive OVLTx or sham operation and were instrumented 1 wk later with telemeters to continuously measure mean arterial pressure (MAP). The following week, rats received a silver clip around the left renal artery to generate 2K1C hypertension or sham-clip surgery. MAP was continuously measured for 6 wk, and once a week, rats were housed in metabolic cages for 24 h to evaluate water intake and urinary volume. Urine was analyzed for inflammatory cytokines and copeptin, a surrogate marker of vasopressin. Neurogenic pressor activity (NPA) was assessed on the last day of the protocol by measuring the peak MAP response to ganglionic blockade. Upon completion of the study, rats were euthanized and kidneys were removed for the measurement of inflammatory cytokine content. Hypertension in 2K1C rats was associated with increased NPA, water intake, vasopressin release, and renal inflammation. All of these responses were markedly attenuated or abolished in OVLTx 2K1C rats. These findings suggest that the OVLT, similar to afferent renal nerves, plays a key role in the development of hypertension, polydipsia, vasopressin release, and renal inflammation in 2K1C-HTN rats.<b>NEW & NOTEWORTHY</b> Renovascular hypertension (RVHT), accounting for 1%-5% of high blood pressure cases, is the most common secondary hypertension resistant to treatment. In two-kidney one-clip (2K1C) hypertensive rats, renal artery stenosis triggers sympathetic nervous system activation, increased vasopressin, water intake, and inflammation. OVLT lesions prevented these responses, similar to afferent renal denervation. This study suggests that OVLT plays a key role in 2K1C hypertension pathogenesis and interacts with afferent renal nerves. Future studies will explore the underlying mechanisms.