Aging and total stenosis triggers differential responses of carotid and basilar arteries to endothelin-1 and phenylephrine

Abstract

Our aim was to investigate the effects of ageing on the vascular contractility of carotid and basilar arteries from guinea-pigs, in a model of total stenosis. Moreover, we attempted to identify whether total stenosis of the left common carotid (stenosed) in adult guinea-pigs, would affect the contractions of contralateral carotid (intact) and basilar arteries to different vasoconstrictors. With this purpose, the left carotid was occluded with a silk thread at a position close to its origin. Vascular reactivity experiments using standard muscle bath were performed 7, 15, 30, and 90 days after carotid occlusion. Reactivity of carotid and basilar arteries to endothelin-1, phenylephrine and KCl was reduced with ageing in naive guinea-pigs. The endothelin-1 and KCl-induced contractions were unaltered in arteries from SHAM-operated animals. Moreover, phenylephrine-induced contractions were reduced in both carotids from 7 days SHAM-operated guinea-pigs, when compared to naive group. Stenosis induced progressive reduction in the contraction induced by endothelin-1, phenylephrine and KCl in the stenosed carotid, when compared to their respective age-matched naive and SHAM groups. Interestingly, an increased contractile-response to vasoconstrictor agents in all the contralateral carotids was observed. Stenosis (30 and 90 days) also induced an increase in the contractions induced by endothelin-1 in the basilar artery. Conversely, phenylephrine and KCl-induced contractions were reduced in basilar arteries 7, 15, 30 and 90 days after stenosis. These results showed that stenosis in adult guinea-pigs induce alterations of vascular reactivity in arteries distant from the site of injury. Thus, in spite of the common use of contralateral carotid as control, it must be aware of the potential alteration induced by stenosis in the vascular motility of such vessels. Additionally, it was verified a relationship between the period of stenosis and the alterations in the vascular reactivity to these vasoconstrictors.

Vascular biology of ageing—Implications in hypertension

“…These findings are paralleled in studies utilising the senescence-accelerated mouse (SAM-P8), which demonstrate increased vascular contractility in response to phenylephrine [42] . Conversely, studies performed on carotid vessels from aged guinea pigs displayed reduced contractile response to both phenylephrine and endothelin-1 (ET-1) compared to younger controls [43] . Thus it appears that differential responses during ageing may differ between species.…”

The effects of aging on the functional and structural properties of the rat basilar artery

“…Also, in another study ET, phenylephrine‐, and KCl‐induced contractions were reduced in basilar and carotid arteries of guinea pigs (de Andrade et al. ). On the other hand, some other researchers have reported that there are no age‐related differences in KCl or 5‐HT contractions of rat cerebral arteries, whereas significant decreases in endothelium‐dependent relaxation to bradykinin or norepinephrine were observed (Arribas et al.…”

“…de Andrade et al. () observed that occlusion of the left carotid artery reduced the contractile response of the stenotic carotid artery, whereas the response in the contralateral carotid and basilar artery was increased with endothelin‐1. In our study, we observed smooth muscle hypertrophy and decreased contractility to ET‐1 and KCl, which is potentially linked to vascular smooth muscle hypertrophy related to changes in the contractile ability.…”