Allergic sensitization increases contractile responses to 5-HT in guinea pig aorta.

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 microM 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.

5-HT Receptor Antagonism Attenuates the Ischemia-Reperfusion Injury After Rabbit Lung Preservation.

The success of lung transplantation is threatened by the appearance of ischemia-reperfusion injury, which is characterized by increased vascular permeability. 5-Hydroxytryptamine (5-HT; serotonin) is known to produce microvascular leakage in the systemic circulation, but its possible role in ischemia-reperfusion injury after lung preservation has not been reported. In this work we measured the release of 5-HT during a 24-hour rabbit lung preservation, and the effect of methiothepin (antagonist of the majority of 5-HT receptors) and SB204741 (antagonist of 5-HT2B/2C receptors) on the modified capillary filtration coefficient (mKf,c) was evaluated at the end of this period. Our results showed that the highest release rate of 5-HT occurred during the first 15 minutes after the lung harvesting and progressively decreased in the following time intervals. The baseline mKf,c greatly increased after 24 hours of lung preservation, and this increment was partially reduced by methiothepin and even more by SB204741. We concluded that 5-HT may play an important role in the ischemia-reperfusion process after lung preservation.

Effect of prostaglandin E2 on the tracheobronchial distribution of lung preservation perfusate.

Complete lung preservation requires the perfusate to reach the cell it intends to protect; this is directly related to the distribution of the preserving solution throughout the lung vasculature. Several prostanoids are clinically used to enhance lung preservation. We evaluated the effect of prostaglandin E2 (PGE2) on the distribution of lung perfusate throughout tracheobronchial tissue. Fourteen pulmonary blocks were procured from an equal number of dogs and divided according to whether or not they had previously received a PGE2 infusion. All lung blocks were perfused with a glucose-insulin-potassium solution, and distribution within the lung parenchyma and tracheobronchial tissue was measured using the flow reference technique and gadolinium-153-labeled microspheres. Once perfusion had taken place, samples of lung parenchyma, tracheobronchial tissue, and flow reference were measured for radioactivity, and flow was calculated per 100 g tissue. Animals receiving PGE2 had an expected 38% decrease in systemic arterial pressure; the duration of infusion of lung perfusate during procurement was shorter in those animals receiving PGE2 (5.75 +/- 0.3 min, vs. no PGE2 8.9 +/- 1.2 min; p < .05). Perfusate flow of bronchial mucosa and cartilage increased by two to three times with the infusion of PGE2 (p < .01). Perfusate flow to lobar bronchus or lung parenchyma was similar in both groups. Flow within the lung parenchyma did not differ statistically when compared to its lobar distribution. In conclusion, PGE2-treated animals had a two- to threefold increase in perfusate flow to mainstem bronchi (including mucosa); these findings to some extent support the rationale for utilizing prostanoids in order to enhance lung preservation in clinical lung transplantation.