Glucagon-like peptide-1 receptor agonists are promising therapeutic agents for the treatment of type 2 diabetes (Knudsen, 2004), but effects other than those on glucoregulation need assessing. The aim of this study was to determine the effects, and possible underlying mechanisms, of 6h infusions of the long-acting glucagon-like peptide-1 receptor agonist, exendin-4 (Nielsen et al., 2004), in conscious rats chronically instrumented for recording regional haemodynamics. Male, Sprague-Dawley rats (400-500g) were implanted with pulsed Doppler flow probes to measure renal (R), mesenteric (M) and hindquarters (H) blood flows. At least 10 days later, catheters were implanted in the caudal artery and jugular vein. All surgery was carried out under general anaesthesia (fentanyl and medetomidine 300μg/kg of each i.p.). Experiments began at least 24h after catheter implantation, in unrestrained, conscious animals. A 6h infusion of exendin-4 (up to 6 pmol/kg/min) had only modest effects on blood pressure, but caused substantial opposing, regionally-selective, vascular effects, and tachycardia (Table 1). Using propranolol (1 mg/kg; 0.5 mg/kg/h) and phentolamine (1 mg/kg; 1 mg/kg/h), a major involvement of beta-adrenoceptors in the vasodilator and cardiac effects was identified, with little or no contribution from alpha-adrenoceptors to the vasoconstriction seen, since the effects of propranolol were not influenced by the additional presence of phentolamine (Table 1). Under conditions where beta-adrenoceptors were antagonised, alone or in combination with alpha-adrenoceptors, or when ganglionic transmission was blocked (pentolinium, 5 mg/kg; 5 mg/kg/h), exendin-4 caused widespread vasoconstriction (Table 1). No role for endogenous angiotensin II, vasopressin, endothelin, neuropeptide Y or prostanoids could be shown in the vasoconstrictor actions of exendin-4 (data not shown). In conclusion, the results show, not only an important beta-adrenoceptor-mediated involvement in the cardiovascular actions of exendin-4 infusion, but also an underlying non-autonomically-mediated vasoconstrictor action, the mechanism of which has not been identified.