Angiotensin AT1 receptor-mediated excitation of rat carotid body chemoreceptor afferent activity

• Published in: The Journal of physiology Vol. 510; no. 3; pp. 773 - 781
• Main Author: Allen, A. M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK The Physiological Society 01.08.1998; Blackwell Science Ltd; Blackwell Science Inc
• Subjects: 1-Sarcosine-8-Isoleucine Angiotensin II - analogs & derivatives; 1-Sarcosine-8-Isoleucine Angiotensin II - metabolism; Angiotensin II - physiology; Angiotensin Receptor Antagonists; Animals; Autoradiography; Carotid Body - physiology; Electric Stimulation; Electrophysiology; Imidazoles - pharmacology; Iodine Radioisotopes; Ligands; Losartan - pharmacology; Male; Membrane Potentials - physiology; Neurons, Afferent - physiology; Original; Patch-Clamp Techniques; Pyridines - pharmacology; Rats; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Receptors, Angiotensin - agonists; Receptors, Angiotensin - physiology
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1111/j.1469-7793.1998.773bj.x

A high density of angiotensin II receptors was observed in the rat carotid body by in vitro autoradiography employing 125 I-[Sar 1 ,Ile 8 ]-angiotensin II as radioligand. Displacement studies demonstrated that the receptors were of the AT 1 subtype. The binding pattern indicated that the AT 1 receptors occurred over clumps of glomus cells, the principal chemoreceptor cell of the carotid body. Selective lesions of the sympathetic or afferent innervation of the carotid body had little effect on the density of receptor binding, demonstrating that the majority of AT 1 receptors were intrinsic to the glomus cells. To determine the direct effect of angiotensin II on chemoreceptor function, without the confounding effects of the vasoconstrictor action of angiotensin II, carotid sinus nerve activity was recorded from the isolated carotid body in vitro . The carotid body was superfused with Tyrode solution saturated with carbogen (95% O 2 , 5% CO 2 ), maintained at 36 °C, and multi-unit nerve activity recorded with a suction electrode. Angiotensin II elicited a dose-dependent excitation of carotid sinus nerve activity (maximum increase of 36 ± 11% with 10 n m angiotensin II) with a threshold concentration of 1 n m . The response was blocked by the addition of an AT 1 receptor antagonist, losartan (1 μ m ), but not by the addition of an AT 2 receptor antagonist, PD123319 (1 μ m ). In approximately 50% of experiments the excitation was preceded by an inhibition of activity (maximum decrease of 24 ± 8% with 10 n m angiotensin II). This inhibitory response was markedly attenuated by losartan but not affected by PD123319. These observations demonstrate that angiotensin II, acting through AT 1 receptors located on glomus cells in the carotid body, can directly alter carotid chemoreceptor afferent activity. This provides a means whereby humoral information about fluid and electrolyte homeostasis might influence control of cardiorespiratory function.