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

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.