Dose-dependent hindquarters vasodilator responses to infusion of human urotensin II (huII) in conscious Sprague-Sawley rats T. Bennett, J.E. March, P.A.Kemp, and S.M. Gardiner. School of Biomedical Sciences, Queen's Medical Centre, Nottingham, NG7 2UH.

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During a 2h infusion of hUII (300 pmol kg^-1 h^-1) slowly-developing pressor, tachycardic and hindquarters vasodilator responses occur (Bennett et al., 2002). Because these effects are incremental, we have now measured the haemodynamic responses to longer term (6h) infusions of a range of hUII doses (0 to 3000 pmol kg^-1 h^-1).

Male Sprague-Dawley rats (400-480g) were anaesthetised (fentanyl and medetomidine, 300µg kg^-1 of each i.p., reversed with nalbuphine and atipamezole, 1 mg kg^-1 of each s.c.) and had pulsed Doppler flow probes and intravascular catheters implanted in a two-stage procedure separated by at least 10 days. Starting 24 h after the last procedure (catheterisation), measurements of mean arterial blood pressure (BP), heart rate (HR), and renal (R), mesenteric (M) and hindquarters (H) vascular conductances (VC) were made in conscious animals. After a period of baseline recording, animals were randomised to receive saline (0.4 ml h^-1 (n=8)) or hUII at doses of 30 (n=9), 300 (n=9) or 3000 (n=8) pmol kg^-1 h^-1. Some of the results are shown in Table 1.

There were no cardiovascular effects associated with administration of saline or hUII (30 pmol kg^-1 h^-1). The pressor and tachycardic effects of UII (300 pmol kg^-1 h^-1) seen at 2h had waned by 6h, whereas the increase in HVC was still significant. Infusion of UII (3000 pmol kg^-1 h^-1) for 2h had no significant pressor effect but there was marked tachycardia and hindquarters vasodilatation; the increases in HR and HVC were still significant at 6h at which time there was an accompanying rise in BP.

Table 1. Cardiovascular effects of saline (SAL) or hUII (300 or 3000 pmol kg^-1 h^-1) infusion . Values for HR (beats min^-1), BP (mmHg) and VC (%) are mean ± s.e.mean, n=7. * P < 0.05 vs baseline (Friedman's test).

One interpretation of these results is that the pressor effect of infusion of hUII (300 pmol kg^-1 h^-1) is due to an increase in cardiac output, which predominates over the hindquarters vasodilatation, but wanes between 2 and 6h. At the higher dose of hUII (3000 pmol kg^-1 h^-1), the greater increase in HVC may offset a rise in BP at 2h, consistent with the finding that as HVC falls (between 2h and 6h) a pressor effect develops.

This work was supported by the British Heart Foundation.

Bennett, T. et al. (2002). Br. J. Pharmacol., 135 (suppl), 200P.