<span style="font-size:11.0pt;font-family: "Times New Roman";mso-fareast-font-family:"Times New Roman";mso-bidi-font-family: Mangal;mso-ansi-language:EN-GB;mso-fareast-language:EN-US;mso-bidi-language: HI" lang="EN-GB">Captopril augments acetylcholine-induced bronchial smooth muscle contractions <i style="mso-bidi-font-style:normal">in vitro</i> via kinin-dependent mechanisms</span>

Abstract

<span style="font-size:11.0pt;font-family: " times="" new="" roman";mso-fareast-font-family:"times="" roman";mso-bidi-font-family:="" mangal;mso-ansi-language:en-gb;mso-fareast-language:en-us;mso-bidi-language:="" hi"="" lang="EN-GB">Angiotensin converting enzyme (ACE) inhibitors therapy is<b style="mso-bidi-font-weight:normal"> </b>a<span style="font-size:11.0pt;font-family:" times="" new="" roman";mso-fareast-font-family:="" "times="" roman";mso-bidi-font-family:mangal;mso-ansi-language:en-us;="" mso-fareast-language:en-us;mso-bidi-language:hi"="" lang="EN-US">associated with bothersome dry cough as an adverse effect. The mechanisms underlying this adverse effect are not clear. Therefore, influence of captopril (an ACE inhibitor) on acetylcholine (ACh)-induced bronchial smooth muscle contractions was investigated. Further, the mechanisms underlying the captopril-induced changes were also explored. <i style="mso-bidi-font-style:normal"><span style="font-size:11.0pt;font-family:" times="" new="" roman";mso-fareast-font-family:="" "times="" roman";mso-bidi-font-family:mangal;mso-ansi-language:en-gb;="" mso-fareast-language:en-us;mso-bidi-language:hi"="" lang="EN-GB">In vitro</span></i><span style="font-size:11.0pt;font-family:" times="" new="" roman";mso-fareast-font-family:="" "times="" roman";mso-bidi-font-family:mangal;mso-ansi-language:en-gb;="" mso-fareast-language:en-us;mso-bidi-language:hi"="" lang="EN-GB"> contractions of rat bronchial smooth muscle to cumulative concentrations of ACh were recorded before and after exposure to captopril. Further, the involvement of kinin and inositol triphosphate (IP₃) pathways for captopril-induced alterations were explored. ACh produced concentration-dependent (5-500 μM) increase in bronchial smooth muscle contractions. Pre-treatment with captopril augmented the ACh-induced contractions at each concentration significantly. Pre-treatment with aprotinin (kinin synthesis inhibitor) or heparin (inositol triphosphate, IP₃-inhibitor), blocked the captopril-induced augmentation of bronchial smooth muscle contractions evoked by ACh. Further, captopril-induced augmentation was absent in calcium-free medium. These results suggest that captopril sensitizes bronchial smooth muscles to ACh-induced contractions. This sensitization may be responsible for dry cough associated with captopril therapy.</span></span></span></span></span>