Role of angiotensin II receptor subtypes in mediating the sympathoexcitatory effects of exogenous and endogenous angiotensin peptides in the rostral ventrolateral medulla of the rabbit.
The pressor region in the rostral part of the ventrolateral medulla (VLM) in the rabbit contains a high density of the AT1 subtype of angiotensin (Ang) II receptor. In this study in anaesthetized barodenervated rabbits, we determined the effect of microinjection into the rostral VLM of the AT1 receptor antagonist losartan and the AT2 receptor antagonist PD123319 on resting arterial pressure and renal sympathetic nerve activity, and on the cardiovascular responses normally evoked by exogenous Ang II or Ang III in this region. Losartan (1 nmol) abolished the pressor and sympathoexcitatory responses normally evoked by exogenous Ang II, but PD123319 (1 nmol) had little effect on these responses. Both losartan (0.1-10 nmol) and PD123319 (0.1-1 nmol) had little effect on the resting arterial pressure and renal sympathetic nerve activity, except for a transient sympathoexcitatory response at the higher doses. In confirmation of previous findings, however, microinjection of the non-selective Ang receptor antagonist [Sar1,Thr8]Ang II (80 pmol) significantly decreased resting arterial pressure and sympathetic nerve activity. These results suggest that the sympathoexcitatory effects evoked by exogenous Ang II and III in the rostral VLM are mediated by AT1 receptors, but that the tonic sympathoexcitation produced by endogenous Ang peptides in the rostral VLM of the rabbit are mediated by receptors other than AT1 or AT2 receptors.
Hirooka
Y
Y
Department of Physiology and Institute for Biomedical Research, University of Sydney, N.S.W., Australia. hyoshi@cardiol.med.kyushu-u.ac.jp
Potts
P D
PD
Dampney
R A
RA
D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology*; D000805:Angiotensin III / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003714:Denervation; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects*; D008845:Microinjections; D011311:Pressoreceptors / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D011817:Rabbits; D011945:Receptors, Angiotensin / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects*
D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D011725:Pyridines; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D000805:Angiotensin III; C073402:PD 123319; C014805:angiotensin II, Sar(1)-Thr(8)-; D019808:Losartan