Sb. Tarpey et al., DIFFERENTIAL-EFFECTS OF ENDOTOXEMIA ON PRESSOR AND VASOCONSTRICTOR ACTIONS OF ANGIOTENSIN-II AND ARGININE-VASOPRESSIN IN CONSCIOUS RATS, British Journal of Pharmacology, 123(7), 1998, pp. 1367-1374
1 Regional haemodynamic responses to arginine vasopressin (AVP; 0.5, 1
.0, 5.0 pmol i.v.) and angiotensin II (AII; 5.0, 10.0, 50.0 pmol i.v.)
were measured in conscious Long Evans rats at various times (0, 2, 6
and 24 h) during infusion of lipopolysaccharide (LPS, 150 mu g kg(-1)
h(-1), i.v., n = 9) or saline (n = 9). Additional experiments were per
formed in vasopressin-deficient (Brattleboro) rats infused with LPS (n
= 7) or saline (n = 8) to determine whether or not, in the absence of
circulating vasopressin, responses to the exogenous peptides differed
from those in Long Evans rats. 2 In the Long Evans rats, during the 2
4 h infusion of LPS, there was a changing haemodynamic profile with re
nal vasodilatation from 2 h onwards, additional mesenteric vasodilatat
ion at 6 h, and a modest hypotension (reduction in mean arterial blood
pressure (MAP) from 103 +/- 1 to 98 +/- 2 mmHg) associated with renal
and hindquarters vasodilatation at 24 h. 3 In the Brattleboro rats, t
he changes in regional haemodynamics during LPS infusion were more pro
found than in the Long Evans rats. At 2 h and 6 h, there was a marked
fall in MAP (from 103 +/- 3 mmHg; to 65 +/- 3 mmHg at 2 h, and to 82 /- 4 mmHg at 6 h) associated with vasodilatation in all three vascular
beds. After 24 h infusion of LPS, the hypotension was less although s
till significant (from 103 +/- 3 mmHg; to 93 +/- 4 mmHg, a change of 1
0 +/- 4 mmHg), and there was renal and hindquarters vasodilatation, bu
t mesenteric vasoconstriction. 4 During infusion of LPS, at each time
point studied, and in both strains of rat, presser responses to AII an
d AVP were reduced, but the changes were less marked at 6 h than at 2
h or 24 h. The reduced presser responses were not accompanied by gener
alized reductions in the regional vasoconstrictor responses. Thus, in
the Long Evans rats, the renal vasoconstrictor responses to both pepti
des were enhanced (at 6 h and 24 h for AVP; at all times for AII), whe
reas the mesenteric vasoconstrictor response to AVP was unchanged at 2
h, enhanced at 6 h and reduced at 24 h. The mesenteric vasoconstricto
r response to AII was reduced at 2 h, normal at 6 h and reduced at 24
h. The small hindquarters vasoconstrictor responses to both peptides w
ere reduced at 2 h and 6 h, but normal at 24 h. 5 In the Brattleboro r
ats, the renal vasoconstrictor responses to both peptides were reduced
at 2 h and enhanced at 6 h and 24 h, whereas the mesenteric vasoconst
rictor response to AVP was normal at 2 h and 6 h, and reduced at 24 h.
The response to AII was reduced at 2 h, normal at 6 h and reduced aga
in at 24 h. There were no reproducible hindquarters vasoconstrictions
to AVP in the Brattleboro rats. The small hindquarters vasoconstrictor
responses to AII were unchanged at 2 h and enhanced at 6 h and 24 h.
6 In isolated perfused mesenteric vascular beds, removed after 24 h of
LPS infusion in vivo, there was an increase in the potency of AVP in
both strains (Long Evans, ED50 saline: 56.9 +/- 15.0 pmol, ED,, LPS: 2
0.4 +/- 4.8 pmol, Brattleboro, ED50 saline: 38.6 +/- 4.2, ED50 LPS: 19
.6 +/- 2.9 pmol), but no change in the responses to AII. 7 These findi
ngs indicate that a reduced presser response to a vasoconstrictor chal
lenge during LPS infusion is not necessarily associated with a reduced
regional vasoconstriction. The data obtained in the Brattleboro rats
indicate a potentially important role for vasopressin in maintaining h
aemodynamic status during LPS infusion in Long Evans rats. However, it
is unlikely that the responses to exogenous AVP (or AII) are influenc
ed by changes in the background level of endogenous vasopressin, since
the patterns of change were similar in Long Evans and Brattleboro rat
s. 8 The results obtained in isolated perfused mesenteric vascular bed
s differed from those in vivo, possibly due to the conditions pertaini
ng with in vitro perfusion.