Is functional upregulation of the 5-HT2B receptor in deoxycorticosterone acetate salt-treated rats blood pressure dependent?
This study tests the hypothesis that the functional upregulation of the arterial 5-hydroxytryptamine (5-HT)2B receptor in arteries of deoxycorticosterone acetate (DOCA)-salt hypertensive rats depends on the development of high blood pressure. Wistar-Furth and Wistar rats were given sham or DOCA-salt treatment (200 mg/kg DOCA, SC; 1.0% NaCl and 0.2% KCI in drinking water). Systolic blood pressures (4 week; mm Hg) were: Wistar Sham (120+/-3), Wistar DOCA (176+/-6), Wistar-Furth Sham (112+/-3) and Wistar-Furth DOCA (136+/-4). Isolated mesenteric arteries from Wistar DOCA and Wistar-Furth DOCA rats displayed a three- to fivefold leftward shift in contraction to 5-HT that was insensitive to blockade by the 5-HT2A receptor antagonist ketanserin (10 nM) and a significantly increased maximal contraction to the 5-HT2B receptor agonist BW723C86 [Wistar DOCA = 90+/-17% phenylephrine contraction; Wistar Sham = 1+/-1%; Wistar-Furth DOCA = 33+/-8%; Wistar-Furth Sham = 0%]. Arteries from Sprague-Dawley rats receiving salt or DOCA alone displayed similar systolic blood pressures (151+/-11 mm Hg and 144+/-5 mm Hg, respectively), but only tissues from rats receiving DOCA displayed an increased contraction to BW723C86 (DOCA alone = 60.7+/-16% vs. sham = 13+/-5.3%). These data suggest that upregulation of the arterial 5-HT2B receptor is largely independent of an increase in blood pressure.
Watts
S W
SW
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824-1317, USA. wattss@pilot.msu.edu
Harris
B
B
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003900:Desoxycorticosterone / Q000494:pharmacology*; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D051381:Rats; D011920:Rats, Inbred WF; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D044403:Receptor, Serotonin, 5-HT2B; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D012965:Sodium Chloride / Q000494:pharmacology*; D015854:Up-Regulation
D044403:Receptor, Serotonin, 5-HT2B; D011985:Receptors, Serotonin; D003900:Desoxycorticosterone; D012965:Sodium Chloride