Captopril increases skin microvascular blood flow secondary to bradykinin, nitric oxide, and prostaglandins.
Angiotensin converting enzyme inhibitors (ACEIs) are a cornerstone of treatment of hypertension and heart failure yet their mechanism of action is still debated. This study was designed to test whether the ACEI captopril increases skin microvascular blood flow by a bradykinin-dependent mechanism. Local changes in microvascular blood flow were measured in the skin of rabbits and of human volunteers using a laser Doppler flow probe. Captopril injected intradermally increased skin blood flow over the dose range of 10(-12)-10(-8) mol site in rabbits and humans. In both species the response was abolished by coinjecting either a nitric oxide synthase (NOS) inhibitor or a cyclooxygenase inhibitor. Intradermal bradykinin also increased rabbit skin microvascular blood flow; at 10(-11) mol site it increased mean +/- SE basal blood flow by 88 +/- 12%. The responses to bradykinin or captopril were abolished by coinjecting a bradykinin antagonist, a specific bradykinin B2 receptor antagonist, or inhibitors of NOS or cyclooxygenase. Injecting a specific angiotensin II receptor antagonist at a dose that antagonized the constrictor effects of exogenous angiotensin II did not cause a significant increase in rabbit skin blood flow. This suggests that endogenous angiotensin II does not influence microvascular blood flow in this model. The results indicate that captopril increases skin microvascular blood flow in rabbits and humans secondary to an increase in endogenous tissue bradykinin; this stimulates B2 receptors with subsequent release of prostaglandins and nitric oxide. ACEIs may increase microvascular perfusion by a bradykinin-dependent mechanism.
Warren
J B
JB
Department of Applied Pharmacology, National Heart and Lung Institute, London, United Kingdom.
Loi
R K
RK
D000328:Adult; D000818:Animals; D001920:Bradykinin / Q000502:physiology*; D065168:Bradykinin Receptor Antagonists; D002216:Captopril / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology*; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply*
D065168:Bradykinin Receptor Antagonists; D011453:Prostaglandins; D009569:Nitric Oxide; D002216:Captopril; D001920:Bradykinin