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.
In rats, neonatal administration of monosodium glutamate (MSG) causes serious damage in some hypothalamic and circumventricular areas. The resulting loss of appropriate neurons important for the regulation of blood pressure (BP) may modulate cardiovascular system receptivity in these animals. In the present study, the reactivity of the cardiovascular system to intravenous injection of ai-adrenergic receptor agonist phenylephrine (200 ^g/kg/ml) and angiotensin II (500 ng/kg in 0.6 ml for 2 min) was investigated in adult rats which had been neonatally treated with MSG or vehicle. BP parameters measured directly in conscious cannulated rats were continuously registered using a computerized system. Under basal conditions, MSG-treated rats had slightly lower systolic, diastolic and mean BP with significant differences in pulse pressure (systolic - diastolic BP). In MSG-treated animals, the maximal increase of mean arterial BP after phenylephrine and the duration of BP elevation after both agents were significantly reduced. Slopes of the linear portion of baroreceptor function curves in control and MSG-treated rats did not differ significantly, indicating that baroreflex efficacy was unchanged. The results obtained by perfusion of the hindlimb vascular bed in situ showed that the pressure responses to increasing doses of noradrenaline in MSG-treated rats were reduced. These findings demonstrate that neonatal treatment of rats with MSG lowers the responsiveness of the cardiovascular system, particularly in response to a-adrenergic stimulation. It is suggested that the attenuation of cardiovascular reactivity in MSG-treated rats is, at least partly, caused by diminished vascular responsiveness.