Pharmacologic and autoradiographic evidence for an up‐regulation of kinin B2 receptors in the spinal cord of spontaneously hypertensive rats
F Cloutier, HS Buck, B Ongali… - British journal of …, 2002 - Wiley Online Library
F Cloutier, HS Buck, B Ongali, R Couture
British journal of pharmacology, 2002•Wiley Online LibraryThe effects of intrathecally (it) injected kinin B1 and B2 receptor agonists and antagonists
were measured on mean arterial pressure (MAP) and heart rate (HR) of conscious
unrestrained spontaneously hypertensive rats (SHR of 16 weeks old) and age‐matched
normotensive Wistar Kyoto (WKY). Quantitative in vitro autoradiographic studies were also
performed on the thoracic spinal cord of both strains with specific radioligands for B2
receptors,[125I]‐HPP‐Hoe 140, and B1 receptors,[125I]‐HPP‐[des‐Arg10]‐Hoe140 …
were measured on mean arterial pressure (MAP) and heart rate (HR) of conscious
unrestrained spontaneously hypertensive rats (SHR of 16 weeks old) and age‐matched
normotensive Wistar Kyoto (WKY). Quantitative in vitro autoradiographic studies were also
performed on the thoracic spinal cord of both strains with specific radioligands for B2
receptors,[125I]‐HPP‐Hoe 140, and B1 receptors,[125I]‐HPP‐[des‐Arg10]‐Hoe140 …
- The effects of intrathecally (i.t.) injected kinin B1 and B2 receptor agonists and antagonists were measured on mean arterial pressure (MAP) and heart rate (HR) of conscious unrestrained spontaneously hypertensive rats (SHR of 16 weeks old) and age‐matched normotensive Wistar Kyoto (WKY). Quantitative in vitro autoradiographic studies were also performed on the thoracic spinal cord of both strains with specific radioligands for B2 receptors, [125I]‐HPP‐Hoe 140, and B1 receptors, [125I]‐HPP‐[des‐Arg10]‐Hoe140.
- Bradykinin (BK) (0.81 – 810 pmol) increased MAP dose‐dependently with increases or decreases of HR. The pressor response to BK was significantly greater in SHR. The cardiovascular response to 8.1 pmol BK was reversibly blocked by 81 pmol Hoe 140 (B2 antagonist) but not by 81 – 810 pmol [des‐Arg10]‐Hoe 140 (B1 antagonist) in both strains.
- The B1 receptor agonist, des‐Arg9‐BK (8100 pmol) produced either no effects or increased MAP with variable effects on HR. These responses were similar in both strains and were reversibly blocked by 81 pmol Hoe 140. Inhibition with 8100 pmol [des‐Arg10]‐Hoe 140 was not specific to B1 agonist‐mediated responses.
- [125I]‐HPP‐Hoe 140 specific binding sites were predominantly located to superficial laminae of the dorsal horn and were significantly higher in SHR. Low levels of [125I]‐HPP‐[des‐Arg10]‐HOE 140 specific binding sites were found in all laminae of both strains.
- It is concluded that the hypersensitivity of the cardiovascular response to BK is due to an increased number of B2 receptors in the spinal cord of SHR and that B1 receptors are unlikely involved in spinal cardiovascular regulation in SHR.
British Journal of Pharmacology (2002) 135, 1641–1654; doi:10.1038/sj.bjp.0704632
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