From the Medical Research Council Multidisciplinary Research Group on
Hypertension, Clinical Research Institute of Montreal, University of Montreal,
Montreal, Quebec, Canada.
Correspondence to Ernesto L. Schiffrin, MD, PhD, FRCPC, Clinical Research Institute of Montreal, 110 Pine Ave W, Montreal, Quebec, Canada H2W 1R7. E-mail schiffe{at}IRCM.Umontreal.ca
Abstract—The structural and
mechanical properties of small arteries are altered in rat models of
hypertension. The precise role of humoral factors in these changes has
not been determined. In deoxycorticosterone acetate (DOCA)–salt
hypertension, endothelin-1 (ET-1) peptide content and gene expression
are enhanced in mesenteric resistance arteries. These vessels also
present augmented vasoconstrictor responsiveness to vasopressin
versus control uninephrectomized rats. To determine whether an
interaction exists between vasopressin and ET-1 in the pathogenesis of
small-artery structural alterations in DOCA-salt rats, we examined the
effect of chronic V1 vasopressin receptor antagonism
(OPC-21268, 30 mg/kg BID) on the structure and mechanical properties of
mesenteric resistance arteries using a pressure myograph and the effect
on preproendothelin-1 (preproET-1) gene expression, determined by
Northern blot analysis of preproET-1 mRNA. Tail-cuff
systolic pressures were elevated in DOCA-salt (200±11
mm Hg) versus uninephrectomized rats (109±4 mm Hg) and
decreased slightly but significantly by OPC-21268 to 187±7 mm Hg
(P<0.01). Treatment with DOCA-salt increased vascular
media-lumen ratios and media cross-sectional areas and reduced both
stress and incremental elastic modulus for a given pressure. However,
there was no change in distensibility or incremental elastic modulus
versus media stress. OPC-21268 partially attenuated the vascular growth
in DOCA-salt rats. PreproET-1 mRNA was increased 2-fold in mesenteric
arteries of DOCA-salt rats versus uninephrectomized rats, an effect
abrogated by OPC-21268. Thus, DOCA-salt hypertension is associated with
altered morphology of the small-arterial wall, without
altering stiffness of the arterial wall components.
OPC-21268 regressed in part these changes, suggesting the involvement
of vasopressin. The concomitant attenuation of enhanced ET-1 expression
by OPC-21268 suggests that ET-1 may be involved in mediating in part
the vascular effects of vasopressin in DOCA-salt hypertensive
rats.
© 1998 American Heart Association, Inc.
Scientific Contributions
Effect of Vasopressin Antagonism on Structure and Mechanics of Small Arteries and Vascular Expression of Endothelin-1 in Deoxycorticosterone Acetate–Salt Hypertensive Rats
Key Words: resistance • mechanics • growth • hypertrophy • remodeling • elastic modulus • endothelin • vasopressin
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