Vasoconstrictor responses to intraluminal and extraluminal 5-hydroxytryptamine (5-HT) were studied in isolated mesenteric resistance arteries of Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Third-order branches of mesenteric arteries were dissected free and mounted on glass cannulae in organ chambers. Changes in intraluminal diameter of the perfused and pressurized vessels were measured. Extraluminal 5-HT (10(-8)-10(-4)M) evoked concentration-dependent contractions that were augmented after removal of the endothelium. The sensitivity of arteries without but not of those with endothelium to 5-HT was increased in SHRs compared to WKY rats. The pA2 value for ketanserin using 5-HT as an agonist was identical in WKY rats and SHRs. The slope of the Schild plots did not significantly differ from 1. Intraluminal 5-HT caused smaller contractions in arteries with endothelium than extraluminal 5-HT. After endothelial removal, the contractions to intraluminal 5-HT were increased. The contraction induced by intraluminal 5-HT in arteries with endothelium was greater in SHRs than WKY rats. Thus, contractile responses to 5-HT are mediated by homogeneous 5-HT2 receptors in rat mesenteric resistance arteries. In SHRs, the affinity of the receptor to 5-HT is not altered. The sensitivity of vascular smooth muscle to 5-HT is increased and the protective role of the endothelium against intraluminal 5-HT is decreased in SHRs.