2011 ASH Program Book - American Society of Hypertension

Special Lecture
Monday, May 23, 2011, 1:30 PM – 4:00 PM • East Ballroom • Third Floor
Robert Tigerstedt Award Lecture
Oscar A. Carretero, MD, FASH
Oscar A. Carretero, MD was born in
Mendoza, Argentina and received his
degree from the School of Medicine at the
University of Cuyo, Mendoza, Argentina.
Dr. Carretero has contributed greatly to
our understanding of the role of vasoactive
hormones in the regulation of blood
pressure and renal function, as well as the
pathogenesis of hypertension and target
organ damage (TOD). His research has
resulted in over 360 publications. His
fundamental contributions began with
his initial hypothesis in 1972 that renal
kinins may be involved in the regulation
of sodium and water excretion, acting as natriuretic and diuretic hormones.
His work has contributed uniquely to the understanding of the
role of the renal kallikrein-kinin system, ranging from the development
of methods to measure the components of the system and its localization
to demonstrating that the renal kallikrein-kinin system is natriuretic and
diuretic not only in high mineralocorticoid situations but also in the basal
state. This work culminated with the demonstration that animals lacking
the main kinin receptor (B2) develop hypertension when they are fed a
high sodium diet. As a pioneer in the field of kinin research, where his
contributions have been fundamental, numerous, and of high quality,
we now understand that kinins act as paracrine hormones, regulating
organ blood flow and renal function, and also participate on the chronic
cardiovascular protective effect of angiotensin-converting enzyme (ACE)
and angiotensin resector blockers. He and his colleagues demonstrated
that kallikrein in the kidney is produced mainly in the connecting tubule
(CNT) and in collaboration with Luciano Barajas they demonstrated that
the CNT returns to the glomerulus and makes contact with the afferent
arteriole. Recently he demonstrated that there is a crosstalk between the
CNT and the afferent arteriole, showing that when sodium is increased
in the perfusate of the CNT, the afferent arteriole dilates. They call this
cross talk between the CNT and the afferent arteriole connecting tubuloglomerular
feedback. This seminal contribution explains why during
a sodium load, renal blood flow increases.
Recently he has made another seminal contribution by demonstrating
that the endogenous tetrapeptide N-Acetyl-Ser-Asp-Lys-Pro (Ac-SDKP);
that is destroyed mainly by ACE; has anti-inflammatory and anti-fibrotic
effects, and also contributes to the cardiovascular and renal protective effect
of ACE inhibitors. Furthermore, he discovered that the enzyme prolyl
oligopeptidase is involved in the release of Ac-SDKP from the protein
thymosin β-4. He has shown that inhibition of this enzyme promotes
vascular and renal fibrosis. He and his group have demonstrated that
this peptide inhibits fibrosis by a) decreasing inflammation, b) fibroblast
proliferation and collagen synthesis, c) TGF expression and d) its TGF
signaling (Smad phosphorylation).
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