| pA2
online © Copyright 2003 The British Pharmacological Society |
006P
University
of Manchester Autumn Meeting September 2003 |
|
Haemodynamic effects of human urotensin II(hUII) in the absence and presence of the corticotropin releasing factor (CRF) receptor antagonist, astressin, in conscious rats
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We have previously reported on some striking similarities between the regional haemodynamic profiles of hUII and CRF in conscious rats (Bennett et al., 2002), and proposed that hUII might release endogenous CRF. Here we tested the hypothesis that some cardiovascular effects of hUII are indirectly mediated by CRF.
Under anaesthesia (fentanyl and medetomidine, 300 µg kg-1 of each i.p. reversed with nalbuphine and atipamezole, 1 mg kg-1 of each s.c.), male, Sprague-Dawley rats (400-450g) had pulsed Doppler flow probes and, at least 14 days later, intravascular catheters, implanted. On the day following catheterisation, measurements of mean arterial blood pressure (MAP), heart rate (HR) and renal (R), mesenteric (M) and hindquarters (H) vascular conductances (VC) were made. Rats were given hUII (3 nmol kg-1 i.v.) 15 min after the onset of astressin (50 µg kg-1 bolus, 50 µg kg-1 h-1; n=10) or saline (0.1ml bolus, 0.4 ml h-1 infusion; n=8) administration. Some of the results are shown in Table 1.
In the absence of astressin, hUII caused a rapid-onset, but short-lived, increase in MVC and biphasic increases in HR and HVC (initial change around 5-10 min post-injection followed by a recovery and a second phase around 90-120 min post-injection). Administration of astressin had no effect on resting cardiovascular variables and did not influence the cardiovascular responses to hUII (Table 1), although CRF (3 nmol kg-1 i.v.)-induced increases in HR (+102±7 beats min-1)MVC (+56±8 [kHz mmHg-1]103) and HVC (+16±3 [kHz mmHg-1]103) were abolished by astressin.
Table
1. Cardiovascular variables before and changes (
)
after hUII in the absence or presence of astressin. Values are mean ±
s.e.mean. Units for VC are (kHz mmHg-1)103.*
P 
0.05 vs baseline
(Friedman's test).
|
Before
|
1
min |
5
min |
90
min |
|
| HR |
325±15
|
+43±5*
|
+84±20*
|
+103±21*
|
| HR +astressin |
356±9
|
35±6*
|
+71±11*
|
+80±14*
|
| MAP |
109±4
|
+9±2*
|
-9±5*
|
+10±3*
|
| MAP +astressin |
105±2
|
+6±1*
|
-6±3
|
+8±3
|
| RVC |
92±9
|
-8±3*
|
-1±3
|
-4±5
|
| RVC +astressin |
80±8
|
-4±1
|
-4±4
|
-4±4
|
| MVC |
82±8
|
+20±3*
|
+20±7*
|
-8±5
|
| MVC +astressin |
101±8
|
+26±3*
|
+26±5*
|
-7±5
|
| HVC |
41±7
|
-2±1
|
+14±4*
|
+19±3*
|
| HVC+astressin |
39±2
|
-2±1
|
+12±3*
|
+21±3*
|
These data do not support the hypothesis that the cardiovascular effects of hUII are mediated by endogenous CRF.
This work was supported by the British Heart Foundation.
Bennett, T. et al. (2002). Br. J. Pharmacol., 135 (suppl), 200P.