PMID- 19660577 OWN - NLM STAT- MEDLINE DCOM- 20100701 LR - 20151119 IS - 1879-3649 (Electronic) IS - 1537-1891 (Linking) VI - 51 IP - 4 DP - 2009 Oct TI - Hyperhomocysteinemia induced by feeding rats diets rich in DL-homocysteine thiolactone promotes alterations on carotid reactivity independent of arterial structure. PG - 291-8 LID - 10.1016/j.vph.2009.07.004 [doi] AB - We aimed to investigate whether hyperhomocysteinemia (HHcy) interferes on carotid vascular reactivity, and how morphological and functional aspects are related. With this purpose male Wistar rats received a solution of dl-homocysteine-thiolactone (1g/kg body weight/day) in the drinking water for 4, 15 and 30 days. Lipid profile, carotid artery-morphology and -responsiveness to acetylcholine, phenylephrine and endothelin-1 were analyzed. Similar increase on homocysteine plasmatic levels occurred in rats treated for 4, 15 and 30 days. High levels of serum cholesterol and triglycerides were observed after HHcy 30 days. Vascular reactivity experiments using standard muscle bath procedures showed that HHcy induced a time-dependent reduction on acetylcholine-induced-relaxation at 4, 15 and 30 days. HHcy enhanced the contractile response of endothelium-intact, but not denuded carotid rings to phenylephrine and endothelin-1, despite the treatment time. Morphometric analysis showed that intimal/medial area ratio was enhanced only at 30 days of HHcy, despite its reduced cell density. The major new finding of the present study is that it establishes a time-course relationship for the events involved on vascular effects associated with HHcy. We demonstrated that alterations on vascular responsiveness precede alterations on arterial structure. Based on such findings it is possible to suggest that vascular dysfunction occurs in early stages while alterations on vessel morphology take place in latest stages of HHcy. FAU - de Andrade, Claudia Roberta AU - de Andrade CR AD - Department of Pharmacology, FMRP-USP, Ribeirao Preto, SP, Brazil. FAU - Tirapelli, Carlos Renato AU - Tirapelli CR FAU - Haddad, Renato AU - Haddad R FAU - Eberlin, Marcos N AU - Eberlin MN FAU - Ramalho, Leandra N Z AU - Ramalho LN FAU - Iyomasa, Mamie M AU - Iyomasa MM FAU - Uyemura, Sergio A AU - Uyemura SA FAU - de Oliveira, Ana Maria AU - de Oliveira AM LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090804 PL - United States TA - Vascul Pharmacol JT - Vascular pharmacology JID - 101130615 RN - 0LVT1QZ0BA (Homocysteine) RN - D5H88XF24X (homocysteine thiolactone) SB - IM MH - Animals MH - Carotid Arteries/drug effects/pathology/*physiology MH - Feeding Methods MH - Homocysteine/administration & dosage/*analogs & derivatives/toxicity MH - Hyperhomocysteinemia/chemically induced/*physiopathology MH - Male MH - Rats MH - Rats, Wistar MH - Vasoconstriction/drug effects/*physiology MH - Vasodilation/drug effects/*physiology EDAT- 2009/08/08 09:00 MHDA- 2010/07/02 06:00 CRDT- 2009/08/08 09:00 PHST- 2009/02/07 00:00 [received] PHST- 2009/05/17 00:00 [revised] PHST- 2009/07/21 00:00 [accepted] PHST- 2009/08/08 09:00 [entrez] PHST- 2009/08/08 09:00 [pubmed] PHST- 2010/07/02 06:00 [medline] AID - S1537-1891(09)00093-7 [pii] AID - 10.1016/j.vph.2009.07.004 [doi] PST - ppublish SO - Vascul Pharmacol. 2009 Oct;51(4):291-8. doi: 10.1016/j.vph.2009.07.004. Epub 2009 Aug 4.