| Abstract | U prvom dijelu studije istražili smo i usporedili vazodilatacijske mehanizme crnog vina u izoliranoj aorti štakora i zamorčića. Acetilkolin uzrokuje snažniju vazodilataciju aortnih prstenova štakora prethodno kontrahiranih noradrenalinom nego u zamorčića, dok je vazodilatacijski učinak crnog vina veći u aortnim prstenovima zamorčića. L-nitro arginin metil ester (L-NAME) u potpunosti inhibira vazodilatacijski učinak vina u aorti štakora dok je u aorti zamorčića učinak vina reduciran za samo 50%. Za istraživanje mehanizama ostatne, L-NAME-a rezistentne vazodilatacije, aortne prstenove zamorčića dodatno smo izložili indometacinu, klotrimazolu i njihovoj kombinaciji. Indometacin je neznačajno reducirao vazodilatacijski učinak vina, dok je u kombinaciji sa L-NAME-om imao sinergistički učinak i smanjio vazodilataciju za 80 %. Nakon izlaganja klotrimazolu, vazodilatacijski učinak vina je smanjen za 25%, a dodavanje indometacina nije uzrokovalo daljnje smanjenje vazodilatacije. Samo kombinacija L-NAME, indometacina i klotrimazola je u potpunosti inhibirala vazodilatacijski učinak vina. Vazodilatacija uzrokovana vinom, u KCl-om prekontrahiranim aortnim prstenovima zamorčića bila je značajno manja (Emax 78.31±6.09%) nego vinom uzrokovana vazodilatacija u noradrenalinom prekontrahiranim prstenovima zamorčića (Emax 126.01±2.11%). L-NAME-a je u potpunosti inhibirala vazodilatacijski učinak vina u KCl-om prekontrahiranim aortnim prstenovima zamorčića. Zaključno, vazodilatacijski odgovor na vino u aorti zamorčića posredovan je s više različitih mehanizama, za razliku od štakorske aorte gdje je vazodilatacijski odgovor posredovan samo NO-om. U drugom dijelu studije istražili smo i usporedili učinke crnog vina na izolirana srca štakora i zamorčića, u bazalnim i uvjetima globalne ishemije i reperfuzije. Vino (0,01 – 3,0 ‰) uzrokuje značajnu vazodilataciju koronarnih arterija u srcu zamorčića što se očituje u nerazmjernom povećanju dopreme kisika u odnosu na potrebe. U srcu štakora primjena vina nije dovela do promjene u promatranim parametrima srčane funkcije. Trideset minutna ishemija u jednakoj mjeri oštećuje funkciju srca zamorčića i štakora. Vino (1‰) smanjuje ishemijsko-reperfuzijska oštećenja srca zamorčića i štakora, ali su protektivni učinci značajno veći u srcu zamorčića. Maksimalni oporavak pulsnog tlaka u odnosu na kontrolne vrijednosti iznosio je: 56% za srca zamorčića izlagana vinu, 43% za netretirana srca zamorčića, 39% za srca štakora izlagana vinu i 38% za netretirana srca štakora. Kontraktura miokarda bila je veća u srcu štakora koju je vino reduciralo u izoliranim srcima obiju vrsta. Srca zamorčića izlagana vinu imala su veći koronarni protok, prije 15,89 ± 1,24 ml/min/g i poslije 11,84 ± 0,94 ml/min/g ishemije, u odnosu na ostale skupine koje se nisu značajno razlikovale i u kojih je iznosio prije ishemije 11,54 ± 0,91ml/min/g, a poslije 6,64 ± 0,89 ml/min/g. Vino je također u većoj mjeri skratilo trajanje ventrikulske fibrilacije tijekom reperfuzije u srcima zamorčića nego u srcima štakora. Zaključno, rezultati izravnih kardiovaskularnih učinaka vina na modelu izoliranih srca i aorte zamorčića i štakora upućuju na značajne razlike među vrstama, kako u bazalnim uvjetima, tako i u odgovoru na vino i uvjete ishemije i reperfuzije. Prema tome, nekritična ekstrapolacija rezultata s jedne vrste na drugu može biti pogrešna. O tome treba osobito misliti kada se radi o složenim tvarima kao što je vino, koje svoje učinke ostvaruje kroz multiple farmakološke putove. |
| Abstract (english) | In the first part of this study we examined and compared mechanisms of the red wine (RW) induced vasorelaxation in guinea pig (GP) and rat aorta. Acetylcholine-induced relaxation of norepinephrine-precontracted aortic rings was stronger in rat than in GP aorta while RW-induced vasorelaxation was stronger in GP aorta. L-nitro arginine methyl ester (L-NAME) abolished RW-induced vasorelaxation in rat aorta, while in GP aorta it was only reduced by 50%. To examine mechanisms of the L-NAME-resistant relaxation, GP aortic rings were additionally exposed to indomethacin, clotrimazole, and their combination. Indomethacin insignificantly reduced RW-induced relaxation, but in combination with L-NAME the relaxation was synergistically decreased (80%). After clotrimazole the relaxation was reduced by 25% and addition of indomethacin caused no further reduction. Only the combination of L-NAME, indomethacin, and clotrimazole prevented RW-induced vasorelaxation. RW-induced vasorelaxation in KCl-precontracted GP rings was significantly smaller (Emax 78.31±6.09%) than the relaxation induced by RW in norepinephrine-precontracted rings (Emax 126.01±2.11%). L-NAME in KCl-precontracted GP rings prevented RW-induced vasorelaxation. In conclusion, different pathways are involved in the RW- induced vasorelaxation in GP aorta, in contrast to rat aorta, in which NO plays main role. In the second part of this study the effects of red wine on isolated rats and guinea pigs hearts were examined and compared in basal conditions and after global ischemia and reperfusion. Wine (0,01 – 3,0‰) induced a significant vasodilatation of coronary arteries in guinea pig heart that resulted in a disproportional increase of oxygen supply compared to demand. In rat heart, appliance of wine did not change observed parameters of heart function. Ischemia equally damaged both rat and guinea pig heart function. Wine (0,01 ‰) decreased ischemia-reperfusion injury of guinea pig and rat hearts, but protective effects were considerably bigger in guinea pig hearts. A maximal recovery of developed pressure compared to baseline values was: 56 % for guinea pigs hearts exposed to wine, 43 % for untreated guinea pig hearts, 39 % for rat hearts exposed to wine and 38 % for untreated rat hearts. The contracture of myocardium was bigger in rat heart and wine reduced contracture in both species. The guinea pig hearts exposed to wine had bigger coronary flow, before 15,89 ± 1,24 ml/min/g and 11,84 ± 0,94 ml/min/g after ischemia, in contrast to the other groups that did not differ mutually, their coronary flow was before 11,54 ± 0,91 ml/min/g, and 6,64 ± 0,89 ml/min/g after ischemia. Also, in guinea pig hearts wine markedly reduced duration of ventricular fibrillation during reperfusion than in rat heart. In summary, the results of direct cardiovascular effects of wine on guinea pig and rat isolated hearts and aorta showed major differences between species in both, basic and ischemia-reperfusion conditions. Therefore, the uncritical extrapolation of the results from one species to another could be misleading. That should be kept in mind, especially in for complex substances, such as wine, whose effects are achieved through multiple pharmacological pathways. |
