Epidemiological and clinical studies suggest that asthma is associated with adverse cardiovascular outcomes, but its mechanism is uncertain. 5-Hydroxytryptamine (5-HT) is a mediator involved in asthma and in cardiovascular functioning. Thus, in the present study, we explored whether allergic sensitization in guinea pigs modifies 5-HT-induced contractile responses and 5-HT2A receptor expression in thoracic aorta rings. We found that sensitization produced a significant increase of 100 µM 5-HT-induced contractions of aorta rings (~27 % greater contraction than in non-sensitized animals, p<0.05). Preincubation with 10 nM ketanserin (a 5-HT2A receptor antagonist) reduced by ~30 % (p=0.003) and ~36 % (p=0.005) the area under the curve of 5-HT-induced contractions in aortas from non-sensitized and sensitized animals, respectively. There were no differences between sensitized and non-sensitized animals with respect to mRNA (qPCR) and protein (Western blot) expression of 5-HT2A receptor in thoracic aortas. We concluded that in this guinea pig model of asthma, allergic sensitization is not confined to airways, but also affects arterial contractile responses to 5-HT; changes in the expression of the 5-HT2A receptor appear not to be involved in this phenomenon.
Asthma poses an increased risk for cardiovascular disorders, suggesting that allergy, which is an underlying process in asthma, causes atypical functioning of organs other than lungs. In a previous study in a guinea pig asthma model, we concluded that allergic sensitization increased aorta contractile responses to 5-HT. To further characterize these responses, here we explored the role of the 5-HT2 receptors family. We found that TCB-2 (5-HT2A agonist) and WAY161503 (5-HT2C agonist) induced aorta contractions resembling those elicited by 5-HT but less intense (~43 % and ~25 %, respectively). In these experiments, aortas from sensitized guinea pigs showed increased contractions to TCB-2, but not to WAY161503. In turn, MDL 100907 (5-HT2A antagonist) and RS-102221 (5-HT2C antagonist) caused a notably and a mild reduction of the 5-HT-induced contractions, respectively, with no differences seen between sensitized and non-sensitized tissues. BW723C86 (5-HT2B agonist) did not induce contractile responses and RS-127445 (5-HT2B antagonist) did not modify the contractile responses to 5-HT. In nonsensitized aortas, the pattern of protein expression of receptors was 5HT2B>5-HT2A=5-HT2C, which did not change in sensitized animals. In conclusion, we found that allergic sensitization increased the aorta contractile responses to 5-HT, partly mediated by enhanced responses of 5-HT2A receptors, which was unrelated to changes in the expression of these receptors.