Pulmonary vasoreactivity in spontaneously hypertensive rats--effects of endothelin-1 and leptin.
BACKGROUND
Systemic hypertension may be associated with an increased pulmonary vascular resistance, which we hypothesized could be, at least in part, mediated by increased leptin.


METHODS
Vascular reactivity to phenylephrine (1 μmol/L), endothelin-1 (10 nmol/L) and leptin (0.001-100 nmol/L) was evaluated in endothelium-intact and -denuded isolated thoracic aorta and pulmonary arteries from spontaneously hypertensive versus control Wistar rats. Arteries were sampled for pathobiological evaluation and lung tissue for morphometric evaluation.


RESULTS
In control rats, endothelin-1 induced a higher level of contraction in the pulmonary artery than in the aorta. After phenylephrine or endothelin-1 precontraction, leptin relaxed intact pulmonary artery and aortic rings, while no response was observed in denuded arteries. Spontaneously hypertensive rats presented with increased reactivity to phenylephrine and endothelin-1 in endothelium-intact pulmonary arteries. After endothelin-1 precontraction, endothelium-dependent relaxation to leptin was impaired in pulmonary arteries from hypertensive rats. In both strains of rats, aortic segments were more responsive to leptin than pulmonary artery. In hypertensive rats, pulmonary arteries exhibited increased pulmonary artery medial thickness, associated with increased expressions of preproendothelin-1, endothelin-1 receptors type A and B, inducible nitric oxide synthase and decreased endothelial nitric oxide synthase, together with decreased leptin receptor and increased suppressor of cytokine signaling 3 expressions.


CONCLUSIONS
Altered pulmonary vascular reactivity in hypertension may be related to a loss of endothelial buffering of vasoconstriction and decreased leptin-induced vasodilation in conditions of increased endothelin-1.
Samantha
S
Gomart
Cécile
C
Damoiseaux
Pascale
P
Jespers
Martine
M
Makanga
Nathalie
N
Labranche
Stéphanie
S
Pochet
Charles
C
Michaux
Guy
G
Berkenboom
Robert
R
Naeije
Kathleen
K
McEntee
Laboratory of Physiology, Faculty of Medicine, Université Libre de Bruxelles, Lennik road 808, 1070 Brussels, Belgium. ldewacht@ulb.ac.be.
Laurence
L
Dewachter
D000818:Animals; D019332:Endothelin-1 / Q000502:physiology*; D006973:Hypertension / Q000503:physiopathology*; D020738:Leptin / Q000502:physiology*; D008297:Male; D009924:Organ Culture Techniques; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology*
D019332:Endothelin-1; D020738:Leptin