Cannabinoid-induced mesenteric vasodilation through an endothelial site distinct from CB1 or CB2 receptors

Cannabinoids, including the endogenous ligand arachidonyl ethanolamide (anandamide), elicit not only neurobehavioral but also cardiovascular effects. Two cannabinoid receptors, CB1 and CB2, have been cloned, and studies with the selective CB1 receptor antagonist SR141716A have implicated peripherally located CB1 receptors in the hypotensive action of cannabinoids. In rat mesenteric arteries, anandamide-induced vasodilation is inhibited by SR141716A, but other potent CB1 receptor agonists, such as HU-210, do not cause vasodilation, which implicates an as-yet-unidentified receptor in this effect. Here we show that “abnormal cannabidiol” (Abn-cbd) is a neurobehaviorally inactive cannabinoid that does not bind to CB1 receptors, yet causes SR141716A-sensitive hypotension and mesenteric vasodilation in wild-type mice and in mice lacking CB1 receptors or both CB1 and CB2 receptors. Hypotension by Abn-cbd is also inhibited by cannabidiol (20 μg/g), which does not influence anandamide- or HU-210-induced hypotension. In the rat mesenteric arterial bed, Abn-cbd-induced vasodilation is unaffected by blockade of endothelial NO synthase, cyclooxygenase, or capsaicin receptors, but it is abolished by endothelial denudation. Mesenteric vasodilation by Abn-cbd, but not by acetylcholine, sodium nitroprusside, or capsaicine, is blocked by SR141716A (1 μM) or by cannabidiol (10 μM). Abn-cbd-induced vasodilation is also blocked in the presence of charybdotoxin (100 nM) plus apamin (100 nM), a combination of K+-channel toxins reported to block the release of an endothelium-derived hyperpolarizing factor (EDHF). These findings suggest that Abn-cbd and cannabidiol are a selective agonist and antagonist, respectively, of an as-yet-unidentified endothelial receptor for anandamide, activation of which elicits NO-independent mesenteric vasodilation, possibly by means of the release of EDHF.

Climate change is affecting altitudinal migrants and hibernating species

Calendar date of the beginning of the growing season at high altitude in the Colorado Rocky Mountains is variable but has not changed significantly over the past 25 years. This result differs from growing evidence from low altitudes that climate change is resulting in a longer growing season, earlier migrations, and earlier reproduction in a variety of taxa. At our study site, the beginning of the growing season is controlled by melting of the previous winter's snowpack. Despite a trend for warmer spring temperatures the average date of snowmelt has not changed, perhaps because of the trend for increased winter precipitation. This disjunction between phenology at low and high altitudes may create problems for species, such as many birds, that migrate over altitudinal gradients. We present data indicating that this already may be true for American robins, which are arriving 14 days earlier than they did in 1981; the interval between arrival date and the first date of bare ground has grown by 18 days. We also report evidence for an effect of climate change on hibernation behavior; yellow-bellied marmots are emerging 38 days earlier than 23 years ago, apparently in response to warmer spring air temperatures. Migrants and hibernators may experience problems as a consequence of these changes in phenology, which may be exacerbated if climate models are correct in their predictions of increased winter snowfall in our study area. The trends we report for earlier formation of permanent snowpack and for a longer period of snow cover also have implications for hibernating species.