CONSEQUENCES OF A HIGH-FAT DIET ON THE REACTIVITY OF THE PULMONARY ARTERY

Introduction Results and Discussions

The traditional renin angiotensin system (RAS) components are: a serum protein On all rings, Aogen 1µM induced contractions were only reduced by pepstatin A (with one third)
prohormone angiotensinogen (Aogen), a proteolytic enzyme, renin, angiotensins (Ang) and or captopril (with at least 35%), amplified by amastatin (with 11,72±7.03%) and totally prevented by
angiotensin receptors (AT). Renin acts on a plasmatic alpha 2-globulin to produce Ang I, losartan. The Aogen contractile effects were powerfully on vessels obtained from OSR (after
which will be transformed by converting enzyme (ACE), on passage through the pulmonary challenge) but these differences were blocked by chimostatin which did not significantly modify
circulation, into the Ang II. Aogen induced contractins on NR. The enzymes effects were not influenced by the the presence or
In the last years many authors proved the existence on tissues of alternative absence of intact endothelium.
(renin and/or ACE independent) pathways of Ang II synthesis forcing the recognition of local
RASs (Richard V et al, 2001).
Both vascular smooth muscle and endothelial cells have been recognized to
generate angiotensins and these data suggested the existence of a vascular RAS that could
modify local vascular function (Gurzu B et al, 2005).
Aimes
In order to investigate the contribution RAS on pulmonary vascular pathology induced
Figure 2. Contraction of rat pulmonary veins induced by Aogen alone and in the presence of 10 M pepstatin A (PepA),
by antigen sensitisation we studied the Aogen – induced contractions on rat pulmonary vein captopril (CAPT), chymostatin (CHY), captopril and chymostatin (CAPT &CHY), amastatin (AMA) and loartan (LOS); n =6;
(RPV) rings from normal (NR) and ovalbumin sensitized rats (OSR) in presence of multiple *: p<0.05 when compared Aogen - induced contractions on OSR (close bars) with NR (open bars).
RAS inhibitors.
Materials and methods Aogen – induced contractions are mediated mainly by type 1 Ang II receptors (as demonstrated by
Sensitization: Male Wistar rats (150–200g) were sensitised against ovalbumin (OVA) by losartan pre-treatment effects). Taking into account that Aogen could not produce vasoconstriction
s.c. and i.p. injection of 0.2 mL physiological saline, containing 100 mg OVA and 8 mg by itself we consider that contractile responses are the result of Aogen degradation to
Al(OH)3. The protocol was repeated 2 weeks later (Cavalher-Machado SC, 2004). vasoconstrictor angiotensins.
Challenge (after 7 days): i.p. injection of 0.2 mL physiological saline, containing 100 mg Pre-treatment with either pepstatin A or captopril only reduced Aogen - induced contractions on
OVA. RPV underlines significance of other enzymatic pathways of Aogen degradation as other authors
Myography: pulmonary veins (RPV) rings were mounted in 2 ml organ baths containing a suggest (Richard V, 2001).
modified Krebs–Henseleit buffer (Dumitriu IL, 2006). After the equilibration period (90 min / Chymostatin did not significantly decreased Aogen – induced contractions on NR, but co-
0.5 g resting tension) the rings were initially stimulated with the standard stimulus (40 mM administering of chymostatin and captopril almost prevented contractile effects of Aogen on RPV of
KCl). Test compounds were added to the organ bath in a maximal volume of 20 µl from OSR.
stock solutions. Amastatin reduces degradation of Ang II (Petrescu G, 2002) leading to higher Ang II local levels
We quantified Aogen – induced contractions in the absence or in the presence (15 minutes that could explain the powerful contractile effects of Aogen on amastatin pre-treated rings.
incubation) of pepstatin A (a renin inhibitor, 10 µM), captopril (an ACE inhibitor, 10 µM), Conclusion
chymostatin (a chymase inhibitor, 10 µM), amastatin (an aminopeptidase-A and -M Our data suggest that pulmonary veins posses a local RAS and there are multiple enzymatic
inhibitor) or losartan (a specific AT1 blocker, 10 µM). pathways for Ang II synthesis than classically described renin – ACE manner. On the other hand,
The results are expressed as the percentage of the control contraction (KCl, 40 mM; mean OVA sensitization generates prominent changes in the components of the vascular RAS,
± S.E.M.). increasing the Ang generation by a chymase – dependent mechanism.

Copyright © 2020
L. G. VATA1, G. Dumitrescu2, B. GURZU3, A. Ceasovschih2, V. SORODOC2, O. SIRBU2, A. STOICA2, R. Haliga2, M. Constantin2, L. SORODOC2; 1University of Medicine and Pharmacy Gr.T Popa Iasi, Internal Medicine, Iasi,
Romania, 2Univestity of Medicine and Pharmacy "Gr. T. Popa", 2'nd Departament of Internal Medicine, Iasi, Romania, 3University of Medicine and Pharmacy Gr.T Popa Iasi, Physiology, Iasi, Romania