Characterization of receptors for angiotensin-induced drinking and blood pressure responses in conscious rats using angiotensin analogs extended at the N-terminal.
Angiotensin II analogs with N-terminal extensions were synthesized to examine their effects on the brain and vascular angiotensin II (Ang II) receptors of the rat. Ang II, Crinia-Ang II, Thr.Ala.Gly-Ang II and Val. Ser.Leu.Thr.Ala.Gly-Ang II were all found to elicit drinking and raise blood pressure when given into the cerebrospinal fluid (CSF), and elevate blood pressure when given intravenously. When given intracerebroventricularly, the order of potency of the peptides in eliciting blood pressure and drinking responses was: Ang II (100%) = Crinia-Ang II (100%) greater than Thr.Ala.Gly-Ang II (10% blood pressure, 15% drinking) greater than Val.Ser.Leu.Thr.Ala.Gly-Ang II (5%). The order of pressor potency did not change when the Ang II analogs were given intravenously, but compared with the central effects, there was a marked difference in the relative potencies of the peptides. The potencies were: Ang II (100%) greater than Crinia-Ang II (80%) greater than Thr.Ala.Gly-Ang II (60%) greater than Val.Ser.Leu.Thr.Ala.Gly-Ang II (20%). Blood pressure and drinking responses produced by all of these peptides were markedly attenuated by the Ang II receptor antagonist, [Sar1,Thr8] Ang II. These findings indicate a difference in the Ang II receptors present in the brain and the periphery. However, no differences were noted between the central Ang II receptors mediating the pressor responses and the central Ang II receptors stimulating drinking behavior.
D000809:Angiotensins / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001808:Blood Vessels / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D004327:Drinking Behavior / Q000187:drug effects*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000187:drug effects*; D011956:Receptors, Cell Surface / Q000187:drug effects*
D000809:Angiotensins; D011945:Receptors, Angiotensin; D011956:Receptors, Cell Surface