title: Influence of pressure on adenosine triphosphate function as a sympathetic neurotransmitter in small mesenteric arteries from the spontaneously hypertensive rat.
abstract: OBJECTIVE
  Enhanced sympathetic neurotransmission contributes to hypertension in the spontaneously hypertensive rat (SHR). We recently reported a method for studying sympathetic neurotransmission in pressurized small arteries, demonstrating a major role of adenosine triphosphate (ATP) as a sympathetic neurotransmitter under these physiological conditions. We have now used this methodology to assess the role of ATP as a sympathetic neurotransmitter in small mesenteric arteries isolated from SHRs.
  
  
  METHODS
  Small arteries were mounted in a suction electrode, cannulated and pressurized to either 30 or 90 mmHg. Nerve-evoked alterations in membrane potential were assessed using sharp microelectrodes. Neurally evoked vasoconstrictor responses were measured in the absence and presence of the α1-adrenoceptor antagonist, tamsulosin (0.1 μmol/l), or the P2 purinoceptor antagonist suramin (0.1 mmol/l).
  
  
  RESULTS
  At 30 mmHg the P2X-receptor-mediated excitatory junctional potential (EJP) was larger in arteries from SHRs (7.9 ± 0.9 mV) than Wistar-Kyoto (WKY) rats (3.2 ± 0.4 mV, P < 0.05). Increasing pressure increased the amplitude of the EJP, which again, was larger in SHRs. At 90 mmHg, activation of the perivascular nerves produced a larger vasoconstriction in arteries isolated from SHRs compared with WKY rats. The vasoconstrictor response in SHRs was abolished by either suramin or tamsulosin.
  
  
  CONCLUSIONS
  These data provide electrophysiological evidence for enhanced purinergic function in the SHR and show that ATP is fundamentally important in contributing to the vasoconstriction produced after activation of the perivascular nerves in pressurized arteries from the SHR. This involves a synergistic interaction with noradrenaline to causes enhanced mesenteric arterial vasoconstriction, which may contribute to the hypertension in this model.
authors.affiliation: Cardiovascular Research Group, School of Biomedical Sciences, University of Nottingham, Nottingham, UK.
authors.forename: Lakshman
authors.initials: L
authors.lastname: Goonetilleke
authors.forename: Vera
authors.initials: V
authors.lastname: Ralevic
authors.forename: William R
authors.initials: WR
authors.lastname: Dunn
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism*; D011312:Pressure; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
chemical_list: D000255:Adenosine Triphosphate