Objectives:

Recently, we reported a novel method to study sympathetic neurotransmission in arteries exposed to an intraluminal pressure (Rummery et al., 2007). In the present study, this method was used to investigate sympathetic neurotransmission in mesenteric small arteries isolated from normotensive (Wistar Kyoto Rat, WKY) and hypertensive (Spontaneous Hypertensive Rat, SHR) rats.

Methods:

Second-order mesenteric arteries isolated from WKY and SHRs were mounted in a perfusion chamber, cannulated and pressurised to 90 mmHg. Neurally evoked contractions in response to electrical field stimulation (EFS) were measured at various frequencies (50 pulses, 0.1 ms pulse width) using a supramaximal voltage. Sympathetic responses were assessed using the a₁ adrenoceptor antagonist, YM12617 (0.1 mM), or the P2X₁ receptor antagonist, NF449 (0.1 mM) added alone.

Results:

The absolute size of the vasoconstrictor response was larger in arteries from SHR (e.g. at 10 Hz, 84 ± 6 mm) compared to WKY rats (31 ± 3 mm, p<0.05, n=21). In WKY rats, the response obtained to 10 Hz stimulation was reduced by 41 ± 6% by YM12617 (n=7, p<0.001) and 53 ± 17% by NF449 (n=5, p<0.01). In SHRs the response to 10 Hz was reduced by 87 ± 6% by YM12617 (n=6, p<0.001) and 59 ± 12% by NF449 (n=7, p<0.001).

Conclusion:

These findings show a larger response to EFS in pressurised mesenteric arteries of SHR compared to WKY rats that may contribute to the hypertension in this strain. NF449 and YM12617 both reduced responses by equivalent amounts in WKY rats indicating the involvement of both noradrenaline (NA) and ATP in mediating the response. Since NF449 and YM12617 each reduced the response in SHR by more than 50%, this suggests a synergistic interaction between NA and ATP in this strain. Rummery, N.M., Brock, J.A., Pakdeechote, P., Ralevic, V. & Dunn, W.R. 2007. J Physiol 582 (Pt2):745–754.