Role of the brain renin-angiotensin system in the maintenance of blood pressure in conscious spontaneously hypertensive and sinoaortic baroreceptor-denervated rats.
1. Evidence suggesting an involvement of the brain renin-angiotensin system (RAS) in the development/maintenance of hypertension in spontaneously hypertensive rats (SHR) relies, in part, on early experimental data reporting centrally mediated antihypertensive effects of saralasin. However, recent data using non-peptide AT1 receptor antagonists does not always support this theory because these compounds usually do not 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 these models exhibit heightened sensitivity to the central pressor effects of angiotensin II (AngII) and, thus, any potential antihypertensive activity would provide functional evidence of activated brain RAS mechanisms in these models. 3. In SHR, saralasin failed to lower mean arterial pressure (MAP) when given intracerebroventricularly (i.c.v.) as bolus or infusion doses that blocked the centrally mediated pressor effect of AngII. 4. In SAD rats, there was a marked impairment of the baroreceptor-heart rate reflex function and enhanced centrally mediated pressor responses to AngII. However, i.c.v. saralasin infusions again did not alter MAP. 5. Collectively, these results suggest that the central 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.
Paull
J R
JR
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
Bunting
M W
MW
Widdop
R E
RE
D000804:Angiotensin II / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D017704:Baroreflex / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology*; D001923:Brain Chemistry / Q000502:physiology*; D003714:Denervation; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D007276:Injections, Intraventricular; D008297:Male; D011311:Pressoreceptors / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012083:Renin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology*; D012504:Saralasin / Q000008:administration & dosage / Q000494:pharmacology; D012849:Sinoatrial Node / Q000502:physiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D012083:Renin; D012504:Saralasin