Abstract P344: Vascular Purinergic Neurotransmission is Not Altered in High Fat-Fed Dahl S Hypertension

Abstract

Mesenteric arteries (MAs) are supplied densely by sympathetic nerves releasing NE and ATP to increase vascular tone. Increased neuronal ATP/NE storage and release and impaired clearance cause hypertension. Our previous studies of DOCA-salt hypertensive rats showed that 1) impairment of the prejunctional autoreceptors regulating ATP and NE release contributes to elevated sympathetic neurotransmission, and 2) purinergic neurotransmission was impaired due to decreased ATP bioavailability in sympathetic nerves. As hyperactivity of sympathetic nerves occurs in obesity-related hypertension, we investigated alterations in purinergic transmission in high fat-fed (HF) Dahl S rats. MAs maintained in vitro were stimulated focally. Intracellular recording of excitatory junction potential (EJP) from smooth muscle cells was obtained from male and female, control and HF rats. EJP amplitude, facilitation and rundown were assessed. EJPs from all groups were abolished by tetrodotoxin (300 nM), a Na + channel blocker, and P2X receptor antagonist, PPADS (10 μM), indicating EJPs were neurogenic and purinergic. At 17 weeks, we found that 1) frequency (0.5-10Hz) response curves from control and HF were similar in male and female arteries. 2) When using short trains of stimulation (0.5Hz; 5 pulses), UK14304 (0.0001-1μM)-, an α2-adrenergic receptor agonist, blocked EJPs response equally well in arteries from control and HF rats. Moreover, the α-adrenergic receptor antagonist, yohimbine (1 μM), potentiated EJPs similarly in control and HF groups. 3) There were no differences in EJP rundown caused by trains of stimulation (10Hz, 50 pulses) in MA from control and HF fed rats. Differential facilitation of purinergic neurotransmission was detected in male vs female. In the presence of yohimbine, degree of EJP facilitation was higher in female arteries compared to male control arteries (2.69±0.26 vs 1.96±0.09 N=4, p<0.05) indicating higher prejunctional ATP storage in female nerves. However, HF did not affect the degree of facilitation. These data suggested that sympathetic neurovascular function is not affected in HF Dahl S rats. Elevated blood pressure in this animal model is not dependent on altered sympathetic neurovascular function.