Role of macrophage inhibitory factor (MIF) in the hypothalamic paraventricular nucleus (PVN) in blood pressure changes induced by hyperosmolality or hypovolemia

Angiotensin II (ANG II) is involved in the CNS mechanisms that control mean arterial pressure (MAP) after hyperosmolality and hypovolemia. MIF in the PVN antagonizes the hypertension evoked by CNS‐injected ANG II or sympathoexcitation induced by a 30% increase in osmolality. Here we investigated the effects of MIF overexpression in the PVN on MAP during a 4% increase in plasma osmolality or hypovolemia. Male SD rats(250–270 g, N=4/group) were implanted with telemetry tranducers into the abdominal aorta, and 10 days later received bilateral injections into the PVN of AAV2‐CBA‐MIF or AAV2‐CBA‐eGFP (1×10 9 gc in 200nl per side) for respective overexpression of MIF or GFP. Two weeks later rats received intragastric NaCl load (2 M NaCl, 2 mL) or hypotensive hemorrhage (4 × 2mL/300 g body wt. blood withdraw, 10 min apart). Throughout the 60 min experimental period, NaCl load elicited increases in MAP in GFP transduced rats (Δ10±2 mmHg vs. baseline; p<0.05) but not in the MIF expressing rats (Δ−4±1 mmHg vs. baseline). Neither the MIF nor the GFP expressing rats completely recovered from hemorrhage‐induced hypotension (Δ−30±13 vs. MIF: −22±6 mmHg, after 60 min; p > 0.05). The results indicate that MIF in the PVN is able to regulate the increases in MAP following increased plasma osmolality, and suggest that the blockade of ANG II actions in the PVN by MIF are not enough to influence the partial recovery of MAP following hemorrhage. Supported by: CNPq, FAPESP, NIH