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

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 B 2 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 B 1 and B 2 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 AT 1 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. B 2 receptor binding sites in most laminae were higher in SHR than in WKY from the age of 8 to 24 wk. Whereas B 1 receptor binding sites were significantly present in young SHR and WKY, they were barely detectable in adult rats. ACEI (16 and 24 wk) and AT 1 antagonist (24 wk) enhanced the number of B 2 without changing B 1 receptor binding sites. However, at 8 wk the three treatments significantly increased B 1 and decreased B 2 receptors in lamina I. It is concluded that 1 ) the higher density of B 2 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 B 1 and B 2 receptors in the rat spinal cord. bradykinin; B 1 receptor; B 2 receptor; hypertension