Vol. 284, Issue 6, H1949-H1958, June 2003
SPECIAL TOPICS
Regulation of Cardiovascular Signaling by Kinins and Products of Similar Converting Enzyme Systems
Chronic
effects of angiotensin-converting enzyme inhibition on kinin receptor
binding sites in the rat spinal cord
Brice
Ongali1,
Hudson de Sousa
Buck1,
Frank
Cloutier1,
Francine
Legault2,
Domenico
Regoli3,
Chantal
Lambert2,
Gaétan
Thibault4, and
Réjean
Couture1
Departments of 1 Physiology,
2 Pharmacology, and 4 Clinical Research
Institute, Université de Montréal, Montréal,
Québec H3C 3J7; Department of 3 Pharmacology,
Université de Sherbrooke, Sherbrooke, Québec,
Canada J1H 5N4
With the use
of in vitro receptor autoradiography, this study aims at determining
whether the higher level of kinin B2 receptor density in
the spinal cord of the spontaneously hypertensive rat (SHR) is
secondary to arterial hypertension and whether chronic treatment with
angiotensin I-converting enzyme inhibitors (ACEI) can regulate neuronal
B1 and B2 receptors. SHR received, from the age
of 4 wk, one of the two ACEI (lisinopril or zofenopril, 10 mg · kg
1 · day
1)
or for comparison, the selective AT1 antagonist (losartan,
20 mg · kg
1 · day
1)
in their drinking water for a period of 4, 12, and 20 wk. Age-matched untreated SHR and Wistar-Kyoto rats (WKY) were used as controls. B2 receptor binding sites in most laminae were higher in
SHR than in WKY from the age of 8 to 24 wk. Whereas B1
receptor binding sites were significantly present in young SHR and WKY,
they were barely detectable in adult rats. ACEI (16 and 24 wk) and
AT1 antagonist (24 wk) enhanced the number of
B2 without changing B1 receptor binding sites.
However, at 8 wk the three treatments significantly increased
B1 and decreased B2 receptors in lamina I. It
is concluded that 1) the higher density of B2
receptors in the spinal cord of SHR is not due to hypertension,
2) kinin receptors are regulated differently by ACEI in
neuronal and vascular tissues, and 3) aging may have a
profound impact on levels of B1 and B2
receptors in the rat spinal cord.
bradykinin; B1 receptor; B2
receptor; hypertension