ROLE OF THE BRAIN RENIN-ANGIOTENSIN SYSTEM IN THE MAINTENANCE OF BLOOD-PRESSURE IN CONSCIOUS SPONTANEOUSLY HYPERTENSIVE AND SINOAORTIC BARORECEPTOR-DENERVATED RATS
Jra. Paull et al., ROLE OF THE BRAIN RENIN-ANGIOTENSIN SYSTEM IN THE MAINTENANCE OF BLOOD-PRESSURE IN CONSCIOUS SPONTANEOUSLY HYPERTENSIVE AND SINOAORTIC BARORECEPTOR-DENERVATED RATS, Clinical and experimental pharmacology and physiology, 24(9-10), 1997, pp. 667-672
1, Evidence suggesting an involvement of the brain renin-angiotensin s
ystem (RAS) in the development/maintenance of hypertension in spontane
ously hypertensive rats (SHR) relies, in part, on early experimental d
ata reporting centrally mediated antihypertensive effects of saralasin
, However, recent data using non-peptide AT(1) receptor antagonists do
es not always support this theory because these compounds usually do n
ot lower blood pressure when given centrally, 2, In the present study
we have re-assessed the central effects of saralasin in conscious SHR
as well as in sinoaortic baroreceptor-denervated (SAD) rats, Both of t
hese models exhibit heightened sensitivity to the central presser effe
cts of angiotensin II (AngII) and, thus, any potential antihypertensiv
e activity would provide functional evidence of activated brain RAS me
chanisms in these models, 3, In SHR, saralasin failed to lower mean ar
terial pressure (MAP) when given intracerebroventricularly (i.c.v.) as
bolus or infusion doses that blocked the centrally mediated presser e
ffect of AngII, 4, In SAD rats, there was a marked impairment of the b
aroreceptor-heart rate reflex function and enhanced centrally mediated
presser responses to AngII. However, i.c.v. saralasin infusions again
did not alter MAP. 5, Collectively these results suggest that the cen
tral RAS is not involved in the maintenance of MAP in SHR and SAD rats
, both of which are models exhibiting a functional hyperresponsiveness
to AngII.