Effects of BW245C, a prostaglandin dp receptor agonist, on systemic and regional haemodynamics in the anaesthetized rat.
1. Prostaglandin D (DP) receptor agonists have been shown to induce hypotension in rat models, possibly via peripheral vasodilation. However, it is not known which tissues and organs are most responsive. 2. In the present study, BW245C, a DP receptor-selective agonist, was administered to Inactin (Sigma, St Louis, MO, USA)-anaesthetized rats. Animals received three serial i.v. infusions (17 min each) of either BW245C (escalating doses of 0.3, 3 and 30 microg/kg; n=6) or vehicle (6% ethanol in normal saline; n=6). Mean arterial pressure (MAP) and heart rate were monitored continuously and regional blood flow was determined by the radionuclide-labelled microsphere method at baseline and at the end of each infusion. 3. It was found that BW245C dose-dependently reduced MAP; blood flow increased in forelimb skeletal muscle and skin, resulting in decreases in the regional vascular resistance (RVR) of skeletal muscle to -6+/-13, -53+/-11 and -68+/-6% of baseline following 0.3, 3 and 30 microg/kg BW245C, respectively (P<0.05 vs vehicle treatment for the two higher doses), and skin to -29+/-8, -55+/-8 (P<0.05) and -30+/-16% of baseline, respectively. Relative to vehicle, blood flow and RVR for brain, heart, lung, liver, stomach and kidney were not significantly affected by BW245C. 4. These results demonstrate that the hypotension resulting from DP receptor activation in the rat is mediated primarily through vasodilation of arterioles of skeletal muscle independent of changes in blood flow to vital organs.
Koch
Kristin A
KA
Neurological Diseases Research, Global Pharmaceutical Research and Development, Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois 60064-6119, USA. kristin.koch@abbott.com
Wessale
Jerry L
JL
Moreland
Robert
R
Reinhart
Glenn A
GA
Cox
Bryan F
BF
D000758:Anesthesia; D018686:Anesthetics, Intravenous / Q000008:administration & dosage; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects*; D006827:Hydantoins / Q000008:administration & dosage / Q000494:pharmacology*; D007262:Infusions, Intravenous; D007274:Injections, Intraperitoneal; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011971:Receptors, Immunologic / Q000819:agonists*; D011982:Receptors, Prostaglandin / Q000819:agonists*; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply / Q000187:drug effects; D013874:Thiopental / Q000008:administration & dosage / Q000031:analogs & derivatives; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D018686:Anesthetics, Intravenous; D006827:Hydantoins; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D014665:Vasodilator Agents; C004316:thiobutabarbital; C030669:BW 245C; D013874:Thiopental; C036293:prostaglandin D2 receptor