Activation of endothelin A receptors contributes to impaired responsiveness of renal mechanosensory nerves in congestive heart failure

• Published in: Canadian journal of physiology and pharmacology Vol. 88; no. 6; pp. 622 - 629
• Main Authors: KOPP, Ulla C, CICHA, Michael Z, JONES, Susan Y
• Format: Conference Proceeding Journal Article
• Language: English
• Published: Plattsburgh, NY National Research Council of Canada 01.06.2010; NRC Research Press; Canadian Science Publishing NRC Research Press
• Subjects: Afferent Pathways - physiopathology; Animals; Antihypertensive Agents - pharmacology; Biological and medical sciences; Congestive heart failure; Diagnosis; Dinoprostone - pharmacology; Disease Models, Animal; Endothelin; Endothelin A Receptor Antagonists; Fundamental and applied biological sciences. Psychology; Heart failure; Heart Failure - pathology; Heart Failure - physiopathology; Hydrostatic Pressure; Kidney - drug effects; Kidney - innervation; Kidney - metabolism; Kidney - physiopathology; Kidney Pelvis - drug effects; Kidney Pelvis - innervation; Kidney Pelvis - metabolism; Kidney Pelvis - physiopathology; Kidneys; Male; Mechanoreceptors - physiology; Myocardium - pathology; Organ Size; Peptides, Cyclic - administration & dosage; Peptides, Cyclic - pharmacology; Perfusion; Properties; Prostaglandins; Rats; Rats, Sprague-Dawley; Receptor, Endothelin A - metabolism; Sodium; Sodium - urine; Studies; Substance P - metabolism; Ventricular Dysfunction, Left - pathology; Ventricular Dysfunction, Left - physiopathology; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Canada; Heart failure; Endothelin; Prostaglandin; Substance P; Arachidonic acid derivatives; Cardiovascular disease; Activation; Neuropeptide; Pressure; Kidney; Vertebrata; Mammalia; Urinary system; Heart disease; Eicosanoid; Tachykinin; Renal nerve; Biological receptor
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/Y10-035

Increasing renal pelvic pressure results in PGE2-mediated release of substance P, leading to increases in afferent renal nerve activity (ARNA) and natriuresis, that is, a renorenal reflex response. The renorenal reflexes are impaired in congestive heart failure (CHF). Impairment of the renorenal reflexes may contribute to the increased renal sympathetic nerve activity and sodium retention in CHF. Endothelin (ET)-1 contributes to the pathological changes in cardiac and renal function in CHF. Therefore, we examined whether the ETA receptor antagonist BQ123 altered the responsiveness of renal mechanosensory nerves in CHF. The ARNA responses to increasing renal pelvic pressure were suppressed in CHF but not in sham-CHF rats. In CHF, increasing renal pelvic pressure by 7.5 mm Hg before and during renal pelvic perfusion with BQ123 increased ARNA 12% +/- 3% and 21% +/- 3% (p < 0.05 vs. vehicle). In isolated renal pelvises from CHF rats, PGE2 increased substance P release from 5 +/- 0 to 7 +/- 1 pg/min without BQ123 and from 4 +/- 1 to 9 +/- 1 pg/min with BQ123 in the bath (p < 0.01 vs. vehicle). BQ123 had no effect on the ARNA responses or substance P release in sham-CHF. In conclusion, activation of ETA receptors contributes to the impaired responsiveness of renal mechanosensory nerves in CHF rats by a mechanism(s) at the renal sensory nerve endings.