Splenic reflex neurohormonal modulation of mesenteric arterial diameter and blood flow

Abstract

Portal hypertension (PH) increases splenic venous pressure and alters splanchnic hemodynamics. We have shown that elevated splenic venous pressure results in a reflex increase in splenic afferent and mesenteric efferent nerve activity. We hypothesized that this neural reflex increases mesenteric arterial tone. In male rats, splenic venous pressure was selectively elevated by partial splenic vein occlusion (SVO). This caused a drop in superior mesenteric arterial blood flow (‐2.0±0.6 mL/min, n=6) which was abolished by splenic denervation (‐0.65±0.3 mL/min, n=5, p<0.05). In separate animals, mesenteric resistance arteries (40‐70μm) were directly visualized with intravital microscopy. Immediately following SVO, mesenteric arterial diameter fell (‐3.1±1.1μm, n=13); this was abolished by splenic denervation (+0.3±0.5μm, n=10, p<0.05), renal denervation (+1.4±0.6μm, n=4, p<0.05) and the angiotensin II AT1 receptor blocker Losartan (+0.45±0.2μm, n=6, p<0.05). Interestingly, mesenteric denervation only attenuated this effect (‐0.2±0.4µm, n=7, p=0.048). We propose that mesenteric arterial tone is modulated primarily by splenorenal reflex mediated release of angiotensin II, with possible contribution from mesenteric angiotensinergic nerves. This initial mesenteric arterial vasoconstriction has implications for initiation of the hyperdynamic circulation of PH. CIHR, AHFMR