Bile acids (BA) are
known to facilitate the absorption of dietary fatty acids, fat soluble vitamins
and maintain cholesterol homeostasis. Recently it has been shown that BA also
interact with other receptors to stimulate various responses for example
affecting vascular tone. This project explores the mechanism of how
taurocholate (a primary BA conjugated with taurine) can induce
vasoconstriction. This can help us understand how conditions like cholestasis
(abnormal BA flow) encourages vascular constriction.
To investigate the
mechanisms of vascular constriction induced by taurocholate.
aorta segments from male Wistar rats were mounted onto a wire myograph, bathed
in physiological salt solution and gassed (95% O2, 5% CO2).
Responses to the cumulative addition of a vasoconstriction agent phenylephrine
(1 nM – 100 ?M) and taurocholate (1 nM – 100 ?M) were measured. To determine
the mechanism behind any taurocholate-induced vasoconstriction, responses to
taurocholate were also performed in the presence of inhibitors for: L-type Ca2+
channel (LTCC); endothelin, muscarinic and thromboxane receptors;
cyclooxygenase (COX) enzyme; organic anion transporter (OAT) and/or OAT
polypeptides; and finally endothelial nitric oxide synthase (eNOS). Responses
were analysed by two-way ANOVA and significance accepted at p