The neuropeptide CRF is involved in the modulation of the baroreflex during hindlimb ischaemia in the anaesthetized rat.
1. The effects of bilateral hindlimb ischaemia (BHLI), and of administration of the neuropeptide corticotrophin-releasing factor (CRF), were tested on cardiovascular variables in propofol-anaesthetized Sprague-Dawley rats. In addition, the effects of antagonizing endogenous CRF on the cardiovascular response to BHLI was investigated. 2. BHLI produced significant increases in mean arterial pressure and heart rate. Baroreflex sensitivity was reduced in all animals tested both 10 and 30 min after the induction of ischemia and this was accompanied by changes which are consistent with an underlying baroreflex resetting. 3. Intracerebroventricular (I.C.V.) administration of CRF (1.5 nmol) produced significant increases in heart rate but not mean arterial pressure. CRF also produced significant reductions in baroreflex sensitivity 10 and 30 min after administration, but there was no consistent evidence of baroreflex resetting. These effects of CRF could be prevented by pretreatment with the synthetic CRF antagonist, alpha-helical CRF(9-41) (alpha hCRF, 6.5 nmol, I.C.V.), which itself had no effect on these cardiovascular variables. 4. Pretreatment with alpha hCRF (6.5 nmol, I.C.V.) prevented the reduction in baroreflex sensitivity observed 10 min after the induction of BHLI, but had no consistent effect on the pressor or tachycardiac responses to BHLI and allowed a clear expression of BHLI-induced baroreflex resetting. alpha-Helical CRF(9-41) had no effect on the reduction in baroreflex sensitivity after 30 min of BHLI. 5. We conclude that corticotrophin-releasing factor mediates, at least in part, the early reduction in baroreflex sensitivity observed during hindlimb ischaemia in the rat.
Turnbull
A V
AV
North Western Injury Research Centre, University of Manchester.
Kirkman
E
E
Rothwell
N J
NJ
Little
R A
RA
D000758:Anesthesia; D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006614:Hindlimb / Q000098:blood supply; D007276:Injections, Intraventricular; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D015742:Propofol; D051381:Rats; D017208:Rats, Wistar
D010446:Peptide Fragments; D003346:Corticotropin-Releasing Hormone; C045089:corticotropin releasing hormone (9-41); D015742:Propofol