The subfornical organ drives hypertension in polycystic kidney disease via the hypothalamic paraventricular nucleus

Aims Hypertension is a prevalent yet poorly understood feature of polycystic kidney disease. Previously, we demonstrated that increased glutamatergic neurotransmission within the hypothalamic paraventricular nucleus produces hypertension in the Lewis Polycystic Kidney (LPK) rat model of polycystic kidney disease. Here, we tested the hypothesis that augmented glutamatergic drive to the paraventricular nucleus in Lewis polycystic kidney rats originates from the forebrain lamina terminalis, a sensory structure that relays blood-borne information throughout the brain. Methods and results Anatomical experiments revealed that 38% of paraventricular nucleus-projecting neurons in the subfornical organ of the lamina terminalis expressed Fos/Fra, an activation marker, in LPK rats while 0.05); treatments that both nevertheless lowered blood pressure in LPK rats (P Conclusion Our data reveal multiple independent mechanisms contribute to hypertension in polycystic kidney disease, and identify high plasma osmolality, angiotensin II type I receptor activation and, importantly, a hyperactive subfornical organ to paraventricular nucleus glutamatergic pathway as potential therapeutic targets.