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Do the cardiovascular effects of angiotensin-converting enzyme (ACE) I involve ACE-independent mechanisms? new insights from proline-rich peptides of Bothrops jararaca.
J Pharmacol Exp Ther. 2007 Aug; 322(2):795-805.JP

Abstract

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 (K(i) = 40,000 and 70,000 nM, respectively), whereas Bj-BPP-10c is a strong bradykinin potentiator and inhibitor of the ACE C site (K(i) = 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 (>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.

Authors+Show Affiliations

Center for Applied ToxinologyCentro de Pesquisa, Inovac çãoe Difusão, Laboratório Especial de Toxinologia Aplicada, Instituto Butantan, Sao Paulo, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17475904

Citation

Ianzer, Danielle, et al. "Do the Cardiovascular Effects of Angiotensin-converting Enzyme (ACE) I Involve ACE-independent Mechanisms? New Insights From Proline-rich Peptides of Bothrops Jararaca." The Journal of Pharmacology and Experimental Therapeutics, vol. 322, no. 2, 2007, pp. 795-805.
Ianzer D, Santos RA, Etelvino GM, et al. Do the cardiovascular effects of angiotensin-converting enzyme (ACE) I involve ACE-independent mechanisms? new insights from proline-rich peptides of Bothrops jararaca. J Pharmacol Exp Ther. 2007;322(2):795-805.
Ianzer, D., Santos, R. A., Etelvino, G. M., Xavier, C. H., de Almeida Santos, J., Mendes, E. P., Machado, L. T., Prezoto, B. C., Dive, V., & de Camargo, A. C. (2007). Do the cardiovascular effects of angiotensin-converting enzyme (ACE) I involve ACE-independent mechanisms? new insights from proline-rich peptides of Bothrops jararaca. The Journal of Pharmacology and Experimental Therapeutics, 322(2), 795-805.
Ianzer D, et al. Do the Cardiovascular Effects of Angiotensin-converting Enzyme (ACE) I Involve ACE-independent Mechanisms? New Insights From Proline-rich Peptides of Bothrops Jararaca. J Pharmacol Exp Ther. 2007;322(2):795-805. PubMed PMID: 17475904.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Do the cardiovascular effects of angiotensin-converting enzyme (ACE) I involve ACE-independent mechanisms? new insights from proline-rich peptides of Bothrops jararaca. AU - Ianzer,Danielle, AU - Santos,Robson Augusto Souza, AU - Etelvino,Gisele Maia, AU - Xavier,Carlos Henrique, AU - de Almeida Santos,Jerusa, AU - Mendes,Elizabeth Pereira, AU - Machado,Leonor Tapias, AU - Prezoto,Benedito Carlos, AU - Dive,Vincent, AU - de Camargo,Antônio Carlos Martins, Y1 - 2007/05/02/ PY - 2007/5/4/pubmed PY - 2007/9/21/medline PY - 2007/5/4/entrez SP - 795 EP - 805 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 322 IS - 2 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 (K(i) = 40,000 and 70,000 nM, respectively), whereas Bj-BPP-10c is a strong bradykinin potentiator and inhibitor of the ACE C site (K(i) = 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 (>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. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/17475904/Do_the_cardiovascular_effects_of_angiotensin_converting_enzyme__ACE__I_involve_ACE_independent_mechanisms_new_insights_from_proline_rich_peptides_of_Bothrops_jararaca_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=17475904 DB - PRIME DP - Unbound Medicine ER -