Mechanisms of angiotensin-induced hypotension and bradycardia in the medial solitary tract nucleus.
The selective angiotensin (ANG) II antagonists losartan (AT1) and CGP-42112A (AT2) were used to determine the receptor subtype and neuronal pathways that mediate the hypotension and bradycardia produced by 200 fmol of ANG II microinjected into the dorsal medial nucleus tractus solitarii (NTS) or dorsal motor nucleus of the vagus (dmnX) in anesthetized rats. At dorsal medial NTS sites (0.3 mm below the surface) where L-glutamate microinjections produced maximal decreases in mean arterial pressure (MAP) and heart rate (HR), ANG II (200 fmol, 50 nl, n = 16) elicited hypotension (-22 +/- 1 mmHg) and bradycardia (-26 +/- 2 beats/min). Although L-glutamate also suppressed respiration, ANG II injections in the medial NTS did not alter respiration. Losartan injected at the medial NTS site caused a dose-dependent reduction of ANG II-induced decreases in MAP and HR. At 2 pmol, the AT1 antagonist attenuated the response to ANG II, whereas 100 pmol abolished the effects of ANG II microinjections. In contrast, the AT2 antagonist CGP-42112A (100 pmol) had no effect on the responses to ANG II. Neither ANG II antagonist altered the cardiovascular effects of L-glutamate injections. Losartan injected into the dmnX blocked hypotension and bradycardia produced by ANG II at that site but did not prevent responses to subsequent ANG II injections in the medial NTS.(ABSTRACT TRUNCATED AT 250 WORDS)
Fow
J E
JE
Department of Neurosciences, Cleveland Clinic Foundation, Ohio 44195-5286.
Averill
D B
DB
Barnes
K L
KL
D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D001919:Bradycardia / Q000209:etiology*; D002319:Cardiovascular System / Q000187:drug effects; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D007022:Hypotension / Q000209:etiology*; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology*; D008845:Microinjections; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology; D014630:Vagus Nerve / Q000502:physiology
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D005971:Glutamates; D007093:Imidazoles; D009842:Oligopeptides; D013777:Tetrazoles; D000804:Angiotensin II; C060894:CGP 42112A; D018698:Glutamic Acid; D019808:Losartan