Enhanced angiotensin-mediated responses in the nucleus tractus solitarii of spontaneously hypertensive rats.
Studies using an AT(1) receptor antagonist, losartan, demonstrated that depressor and bradycardic responses to angiotensin II (Ang II) injection into the nucleus tractus solitarii (NTS) are mediated via those receptors. We further characterized Ang II-evoked cardiovascular responses in this nucleus in spontaneously hypertensive rats (SHR) using a new, selective AT(1) receptor antagonist, valsartan. In alpha-chloralose-anesthetized Sprague-Dawley (S-D) rats, Wistar-Kyoto (WKY) rats, and SHR, unilateral injection of Ang II into the NTS decreased arterial pressure (AP) and heart rate (HR). This response was eliminated by preinjection of valsartan. Depressor responses were much greater in SHR than in WKY rats. In normotensive rats, bilateral valsartan injection did not alter baseline AP or HR, or baroreceptor reflex index (BRI) calculated as the maximal change in HR (bpm) divided by phenylephrine- or nitroprusside-induced maximal change in mean AP (mmHg). In SHR, this treatment did not alter baseline HR and BRI, but significantly increased AP. Preinjection of valsartan did not alter injected glutamate effects in any strain. Thus, stimulation of AT(1) receptors within the NTS contributes to cardiovascular regulation independently of the baroreceptor reflex and the glutamatergic system. This angiotensinergic system in SHR acts tonically to reduce AP.
Katsunuma
Nobuhide
N
Second Department of Internal Medicine, Nihon University School of Medicine, 30-1, Oyaguchi-Kamichou, Itabashi-ku, Tokyo 173-8610, Japan.
Tsukamoto
Kazuyoshi
K
Ito
Satoru
S
Kanmatsuse
Katsuo
K
D000804:Angiotensin II / Q000502:physiology*; D000809:Angiotensins / Q000502:physiology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007839:Functional Laterality; D018698:Glutamic Acid / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D017552:Solitary Nucleus / Q000187:drug effects* / Q000502:physiology; D013045:Species Specificity; D013777:Tetrazoles / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
D000809:Angiotensins; D000959:Antihypertensive Agents; D013777:Tetrazoles; D000804:Angiotensin II; D018698:Glutamic Acid; D000068756:Valsartan; D014633:Valine