title: Effects of portal hypertension on contractility of rat spleen.
abstract: Portal hypertension induces changes in vascular responses to vasoconstrictors. However, the effects of portal hypertension on splenic contraction have not previously been investigated. In partial portal vein ligated (PVL) and sham-operated rats, we examined the splenic contractile responses to cumulative concentrations of noradrenaline and KCl. In PVL rats, the potency of noradrenaline in producing splenic contraction was significantly increased (pEC50 of 5.88 ± 0.08), as compared to sham (5.40 ± 0.06; p<0.001). In the presence of prazosin (10(-8)M), there was a significant rightward shift in the noradrenaline concentration response curve but the shift was greater for PVL, so that in the presence of prazosin there was no significant difference between PVL and sham animals in the potency of noradrenaline. Prazosin produced a significantly greater shift of noradrenaline potency in spleen from PVL (pKB of 8.88 ± 0.06) (n=6) than from sham animals (8.51 ± 0.08, n=6), demonstrating that the α1-adrenoceptor mediated component is greater in spleen from PVL. In the presence of prazosin (10(-8)M) the residual response is non-α1-adrenoceptor mediated, presumably α2-adrenoceptor mediated, and this response did not differ between sham and PVL. The maximum splenic contraction did not significantly differ between sham and PVL rats for either agonist. In conclusion, noradrenaline potency in contracting the rat spleen was significantly increased in tissues from PVL rats. The increased potency of prazosin suggests a greater predominance of α1-adrenoceptors in spleen of PVL rats, as prazosin has lower potency at α2-adrenoceptors.
authors.affiliation: Liver Unit, St. Vincent's University Hospital, University College Dublin, Elm Park, Dublin 4, Ireland; Department of Physiology, Royal College of Surgeons in Ireland, 123, St. Stephen's Green, Dublin 2, Ireland.
authors.forename: Jun Liong
authors.initials: JL
authors.lastname: Chin
authors.forename: P
authors.initials: P
authors.lastname: Aiden McCormick
authors.forename: James R
authors.initials: JR
authors.lastname: Docherty
mesh_terms: D000818:Animals; D006975:Hypertension, Portal / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*
chemical_list: D011189:Potassium Chloride; D009638:Norepinephrine; D011224:Prazosin
keywords: Noradrenaline; Portal hypertension; Portal hypertensive rat; Splenic contraction