The metalloproteinase ADAM10 sheds angiotensin-converting enzyme (ACE) from the pulmonary endothelium as a soluble, functionally active convertase.

The renin-angiotensin-aldosterone system (RAAS) plays a critical role in the regulation of blood pressure and fluid balance, with angiotensin-converting enzyme (ACE) being a key transmembrane enzyme that converts angiotensin I to angiotensin II. Hence, ACE activity is an important drug target in cardiovascular pathologies such as hypertension. Our study demonstrates that human pulmonary microvascular endothelial cells (HPMECs) are an important source of proteolytically released ACE.

Amitriptyline inhibits bronchoconstriction and directly promotes dilatation of the airways.

Introduction: The standard therapy for bronchial asthma consists of combinations of acute (short-acting ß-sympathomimetics) and, depending on the severity of disease, additional long-term treatment (including inhaled glucocorticoids, long-acting ß-sympathomimetics, anticholinergics, anti-IL-4R antibodies). The antidepressant amitriptyline has been identified as a relevant down-regulator of immunological T2-phenotype in asthma, acting-at least partially-through inhibition of acid sphingomyelinase (ASM), an enzyme involved in sphingolipid metabolism. Here, we investigated the non-immunological role of amitriptyline on acute bronchoconstriction, a main feature of airway hyperresponsiveness in asthmatic disease.