Bradykinin and matrix metalloproteinases are involved the structural alterations of rat small resistance arteries with inhibition of ACE and NEP

Damiano Rizzoni, Gian Paolo Rossi, Enzo Porteri, Daniele Sticchi, Luigi Rodella, Rita Rezzani, Intissar Sleiman, Carolina De Ciuceis, Silvia Paiardi, Rossella Bianchi, G. G. Nussdorfer, Enrico Agabiti-Rosei

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background and aim: Increased vascular resistance is a hallmark of hypertension and involves structural alterations, which may entail smooth muscle cell hypertrophy or hyperplasia, or qualitative or quantitative changes in extracellular matrix (ECM) proteins. Since the renin-angiotensin-aldosterone system modulates these changes, we investigated the effects of 8 weeks of treatment with an angiotensin-converting enzyme (ACE) inhibitor, ramipril (RAM), or a dual ACE and neutral endopeptidase (NEP) inhibitor, MDL-100240 (MDL), on mesenteric small artery structure and ECM proteins in mRen2-transgenic rats (TGRs), an animal model of hypertension with severe cardiovascular damage. Materials and methods: Thirty-five 5-week-old rats were included in the study: six TGRs received RAM; five TGRs RAM + the bradykinin receptor inhibitor, icatibant; six TGRs, MDL; and five TGRs MDL+ icatibant, while eight TGRs and five normotensive Sprague-Dawley controls were kept untreated. Mesenteric small arteries were dissected and mounted on a micromyograph. The mediato-lumen ratio (M/L) was then calculated. Vascular metalloproteinase (MMP) content was evaluated by zymography. Results: In untreated TGRs severe hypertension was associated with inward eutrophic remodelling of small arteries. Both RAM and MDL prevented the increase in blood pressure and M/L and decreased MMPs. Icatibant blunted the effect of MDL on BP, M/L and MMPs. Conclusions: Changes in collagenase activity induced by ramipril and MDL are associated with prevention of small artery structural alterations in TGRs. Furthermore, MDL-induced enhancement of bradykinin could play a role in both the prevention of vascular structural alterations and in the stimulation of MMPs.

Original languageEnglish
Pages (from-to)759-766
Number of pages8
JournalJournal of Hypertension
Volume22
Issue number4
DOIs
Publication statusPublished - Apr 2004

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Transgenic Rats
Neprilysin
Bradykinin
Peptidyl-Dipeptidase A
Matrix Metalloproteinases
Ramipril
Arteries
Mesenteric Arteries
Extracellular Matrix Proteins
Hypertension
Blood Vessels
Genetically Modified Animals
Metalloproteases
Collagenases
Renin-Angiotensin System
Protease Inhibitors
Angiotensin-Converting Enzyme Inhibitors
Vascular Resistance
Hypertrophy
Smooth Muscle Myocytes

Keywords

  • Drugs
  • Hypertension
  • Hypertrophy
  • Remodelling
  • Vessels

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology

Cite this

Bradykinin and matrix metalloproteinases are involved the structural alterations of rat small resistance arteries with inhibition of ACE and NEP. / Rizzoni, Damiano; Rossi, Gian Paolo; Porteri, Enzo; Sticchi, Daniele; Rodella, Luigi; Rezzani, Rita; Sleiman, Intissar; De Ciuceis, Carolina; Paiardi, Silvia; Bianchi, Rossella; Nussdorfer, G. G.; Agabiti-Rosei, Enrico.

In: Journal of Hypertension, Vol. 22, No. 4, 04.2004, p. 759-766.

Research output: Contribution to journalArticle

Rizzoni, D, Rossi, GP, Porteri, E, Sticchi, D, Rodella, L, Rezzani, R, Sleiman, I, De Ciuceis, C, Paiardi, S, Bianchi, R, Nussdorfer, GG & Agabiti-Rosei, E 2004, 'Bradykinin and matrix metalloproteinases are involved the structural alterations of rat small resistance arteries with inhibition of ACE and NEP', Journal of Hypertension, vol. 22, no. 4, pp. 759-766. https://doi.org/10.1097/00004872-200404000-00019
Rizzoni, Damiano ; Rossi, Gian Paolo ; Porteri, Enzo ; Sticchi, Daniele ; Rodella, Luigi ; Rezzani, Rita ; Sleiman, Intissar ; De Ciuceis, Carolina ; Paiardi, Silvia ; Bianchi, Rossella ; Nussdorfer, G. G. ; Agabiti-Rosei, Enrico. / Bradykinin and matrix metalloproteinases are involved the structural alterations of rat small resistance arteries with inhibition of ACE and NEP. In: Journal of Hypertension. 2004 ; Vol. 22, No. 4. pp. 759-766.
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AU - Rizzoni, Damiano

AU - Rossi, Gian Paolo

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AU - Sticchi, Daniele

AU - Rodella, Luigi

AU - Rezzani, Rita

AU - Sleiman, Intissar

AU - De Ciuceis, Carolina

AU - Paiardi, Silvia

AU - Bianchi, Rossella

AU - Nussdorfer, G. G.

AU - Agabiti-Rosei, Enrico

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