Haemodynamic effects of the endocannabinoid anandamide in conscious rats with acute hypertension

W.-S. Vanessa Ho, Sheila M. Gardiner. University of Nottingham, Nottingham, United Kingdom.

A triphasic blood pressure response to anandamide has been described, the third phase of which, a depressor response, reportedly occurs only in anaesthetised, normotensive rats and in conscious, hypertensive rats (Lake et al., 1997) In this context, to date, only chronic models of hypertension have been studied. We have now assessed the cardiovascular effects of anandamide (1 and 3 mg kg-1, i.v.) in rats made acutely hypertensive by infusion of angiotensin II (AII; 500 ng kg-1h-1) and arginine vasopressin (AVP; 50 ng kg-1 h-1). Male Wistar rats (350–450 g; Charles River, UK) were implanted with miniaturised pulsed Doppler flow probes and catheters as described previously (Gardiner et al., 2002). On the day of experiment, animals received continuous i.v. infusion of either saline or AII plus AVP, followed by bolus injection (0.12 ml, i.v.) of anandamide 105 min later. Data are shown as mean ± SEM. Infusion of AII and AVP significantly (P<0.05, Mann-Whitney U test) increased mean arterial blood pressure (BP; 154 ± 3 vs 114 ± 2 mmHg), reduced vascular conductance (VC) in renal (RVC; 47 ± 4 vs 81 ± 4), mesenteric (MVC; 20 ± 3 vs 62 ± 5) and hindquarter beds (HVC; 12 ± 1 vs 39 ± 2 (kHz mm Hg-1)x103) and reduced heart rate (HR; 217 ± 12 vs 359 ± 11 beats min-1). Responses to anandamide are shown in Table 1.

This study, for the first time, demonstrates that anandamide causes dose-dependent depressor and vasodilator effects in hypertensive, conscious rats.

Gardiner SM et al. (2002) Br J Pharmacol 135: 1889-96

Lake KD et al. (1997) Hypertension 29:1204-10

This study was supported by the British Heart Foundation and Anne McLaren Fellowship