TY - JOUR T1 - Do the Cardiovascular Effects of Angiotensin-Converting Enzyme (ACE) I Involve ACE-Independent Mechanisms? New Insights from Proline-Rich Peptides of <em>Bothrops jararaca</em> JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 795 LP - 805 DO - 10.1124/jpet.107.120873 VL - 322 IS - 2 AU - Danielle Ianzer AU - Robson Augusto Souza Santos AU - Gisele Maia Etelvino AU - Carlos Henrique Xavier AU - Jerusa de Almeida Santos AU - Elizabeth Pereira Mendes AU - Leonor Tapias Machado AU - Benedito Carlos Prezoto AU - Vincent Dive AU - Antônio Carlos Martins de Camargo Y1 - 2007/08/01 UR - http://jpet.aspetjournals.org/content/322/2/795.abstract N2 - Angiotensin-converting enzyme (ACE) inhibitors were developed based on proline-rich oligopeptides found in the venom of Bothrops jararaca (Bj) previously known as bradykinin-potentiating peptides (BPPs). However, the exact mechanism of action of BPPs remains unclear. The role of the ACE in the cardiovascular effects of two of naturally proline-rich oligopeptides (Bj-BPP-7a and Bj-BPP-10c) was evaluated in vitro and in vivo. Bj-BPP-7a does not potentiate the cardiovascular response to bradykinin and is a weak inhibitor of ACE C and N sites (Ki = 40,000 and 70,000 nM, respectively), whereas Bj-BPP-10c is a strong bradykinin potentiator and inhibitor of the ACE C site (Ki = 0.5 versus 200 nM for N site). Strikingly, both peptides, in doses ranging from 0.47 to 71 nmol/kg, produced long-lasting reduction (&gt;6 h) in the mean arterial pressure of conscious spontaneously hypertensive rats (maximal change, 45 ± 6 and 53 ± 6 mm Hg for Bj-BPP-7a and Bj-BPP-10c, respectively). The fall in blood pressure was accompanied by variable degrees of bradycardia. In keeping with the absence of relationship between ACE-inhibitory and antihypertensive activities, no changes in the pressor effect of angiotensin I or in the hypotensive effect of bradykinin were observed at the peak of the cardiovascular effects of both peptides. Our results indicate that the antihypertensive effect of two Bj-BPPs containing the motif Ile-Pro-Pro is unrelated to their ability for inhibiting ACE or potentiating bradykinin (BK), indicating as a major component ACE and BK-independent mechanisms. These results are in line with previous observations suggesting ACE inhibition-independent mechanisms for angiotensin I-converting enzyme inhibitor. The American Society for Pharmacology and Experimental Therapeutics ER -