Angiotensin II Enhances Responses to Endothelin-1 in Bovine Bronchial Smooth Muscle

✍ Scribed by J.E. Nally; R.A. Clayton; M.J.O. Wakelam; N.C. Thomson; J.C. McGrath

• Publisher: Elsevier
• Year: 1994
• Tongue: English
• Weight: 243 KB
• Volume: 7
• Category: Article
• ISSN: 0952-0600
• DOI: 10.1006/pulp.1994.1048

✦ Synopsis

SUMMARY: Angiotensin II and endothelin-1 are putative mediators in asthma. In this study we have examined the effect of angiotensin II on endothelin-1-induced contractions in bovine bronchi and the receptor types involved in the response to these agonists. Angiotensin II alone is very low in potency, producing only small contractions. In the presence of angiotensin II (10^{-7}) or (3 \times 10^{-7} \mathrm{M}), contractions evoked by endothelin-1 were markedly enhanced. The (\mathbf{A I I}{1})-receptor antagonist, losartan, abolished this enhancement suggesting that angiotensin II exerts this effect via an (\mathrm{AII}{1})-receptor. The contraction evoked by endothelin-1 is mediated via an (\mathbf{E t}{\mathrm{A}})-receptor subtype since the (\mathbf{E t}{A})-receptor antagonist FR139317 attenuated the response. This is offset by an inhibitory (\mathbf{E t}{B})-type receptor, resulting in a larger contraction when these receptors are desensitized. Indeed, the (\mathbf{E t}{\mathrm{B}})-receptor agonist sarafotoxin S6c reversed methacholine-evoked tone in a concentration-dependent manner. In conclusion, angiotensin II potentiates contractions evoked by endothelin-1 in bovine bronchi. This may be a mechanism by which angiotensin II-which has little activity in bronchi-may evoke substantial changes in airway tone. Angiotensin II evokes this potentiation via (\mathbf{A I}{1})-receptors, whilst endothelin-1 evokes contraction via (\mathbf{E t}{A})-receptors, an action which is offset by an inhibitory effect of (\mathbf{E t}_{B})-receptors.