Objectives: 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.
Conclusion: 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.
Cardiovascular Research Group, School of Biomedical Sciences, University of Nottingham, Nottingham, UK
Correspondence to Dr William Dunn, School of Biomedical Sciences, University of Nottingham, Nottingham NG7 2UH, UK. Tel: +44 0 115 823 0188; fax: +44 0 115 823 0142; e-mail: firstname.lastname@example.org
Abbreviations: EFS, electrical field stimulation; EJP, excitatory junctional potential; FRC, frequency-response curve; SHR, spontaneously hypertensive rat; WKY, Wistar–Kyoto
Received 18 July, 2012
Revised 12 October, 2012
Accepted 24 October, 2012