Arachidonate metabolites and serotonin contraction of femoral arteries from DOCA-salt hypertensive rats.
Serotonin stimulates phospholipase A(2)(PLA(2)) leading to the production of prostaglandin products, several of which are vasoconstrictors. We hypothesised that the elevated vascular responsiveness to serotonin in deoxycorticosterone acetate (DOCA)-hypertensive rats is due in part to augmented production of vasoconstrictor cyclooxygenase products (e.g. PGF(2)alpha). Denuded helical strips of femoral arteries from DOCA-salt hypertensive rats (SBP 183 +/- 7 mmHg) and normotensive control rats (SBP 115 +/- 2) were used in all experiments. EC(50) values for several agonists were significantly reduced in DOCA arteries compared with controls (in mu mol/L, control vs. DOCA): PGF(2)alpha (0.99 vs. 0.23), PGE(2) (0.72 vs. 0.22), arachidonate (1.52 vs. 0.73), serotonin (0.19 vs. 0.07), noradrenaline (0.029 vs. 0.013), KCl (40.1 vs. 27.0 mmol/L) and AlF(4) (2.3 vs. 1.4 mmol/L). Treatment with indomethacin (14 mu mol/L) inhibited the responses to serotonin in DOCA arteries (EC(50) values 0.07 untreated vs. 0.70) and eliminated the responses to arachidonate but did not affect KCl or AlF(4-)contractions. Cyclooxygenase inhibitors shifted concentration response curves to serotonin in sham and DOCA tissues equally. Thus increased sensitivity to serotonin in DOCA arteries persisted following cyclooxygenase blockade. Therefore, although arachidonate products contribute to the serotonergic contraction in femoral arteries, the augmented response in arteries from DOCA hypertensive rats is not due to increased production of or sensitivity to cyclooxygenase products. Furthermore,arachidonate metabolites do not contribute to the contraction induced by either AlF(4-)or KCl in this preparation.
Kanagy
N L
NL
Department of Physiology, University of New Mexico, Albuquerque, NM, USA.
Mecca
T E
TE
Webb
R C
RC
D017607:Aluminum Compounds / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003900:Desoxycorticosterone; D004353:Drug Evaluation, Preclinical; D005263:Femoral Artery / Q000187:drug effects*; D005459:Fluorides / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced*; D016015:Logistic Models; D008297:Male; D010741:Phospholipases A / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology*; D012965:Sodium Chloride; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D017607:Aluminum Compounds; D016861:Cyclooxygenase Inhibitors; D014662:Vasoconstrictor Agents; D016718:Arachidonic Acid; D012701:Serotonin; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D011189:Potassium Chloride; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D005459:Fluorides; C032311:aluminum fluoride