Pharmacological characterization of the cardiovascular responses elicited by kinin B1 and B2 receptor agonists in the spinal cord of streptozotocin-diabetic rats

1 Kinin receptor agonists and antagonists at the B-1 and B-2 receptors were injected intrathecally (i.t., at T-9 spinal cord level) to conscious unrestrained rats and their effects on mean arterial pressure (MAP) and heart rate (HR) were compared in streptozotocin (STZ)-diabetic rats (65 mg kg(-1) STZ, i.p. 3 weeks earlier) and aged-matched control rats. 2 The B-1 receptor agonist, des-Arg(9)-Bradykinin (BK) (3.2-32.5 nmol), evoked dose-dependent increases in MAP and tachycardia during the first 10 min post-injection in STZ-diabetic rats only. The cardiovascular response to 6.5 nmol des-Arg(9)-BK was reversibly blocked by the prior i.t. injection of antagonists for the B-1 receptor ([des-Arg(10)]-Hoe 140, 650 pmol or [Leu(8)]-des-Arg(9)-BK, 65 nmol) and B-2 receptor (Hoe 140, 81 pmol or FR173657, 81 pmol) or by indomethacin (5 mg kg(-1), i.a.). 3 The i.t. injection of BK (8.1-810 pmol) induced dose-dependent increases in MAP which were accompanied either by tachycardiac (STZ-diabetic rats) or bradycardiac (control rats) responses. The presser response to BK was significantly greater in STZ-diabetic rats. The cardiovascular response to 81 pmol BK was reversibly blocked by 81 pmol Hoe 140 or 81 pmol FR173657 but not by B-1 receptor antagonists nor by indomethacin in STZ-diabetic rats. 4 The data suggest that the activation of kinin B-1 receptor in the spinal cord of STZ-diabetic rats leads to cardiovascular changes through a prostaglandin mediated mechanism. Thus, this study affords an accessible model for studying the expression, the pharmacology and physiopathology of the B-1 receptor in the central nervous system.