Hypotensive effect of ANG II and ANG-(1-7) at the caudal ventrolateral medulla involves different mechanisms.
The objective of the present study was to determine the contribution of the autonomic nervous system and nitric oxide to the depressor effect produced by unilateral microinjection of ANG-(1-7) and ANG II into the caudal ventrolateral medulla (CVLM). Unilateral microinjection of ANG-(1-7), ANG II (40 pmol), or saline (100 nl) was made into the CVLM of male Wistar rats anesthetized with urethane before and after intravenous injection of 1) methyl-atropine, 2.5 mg/kg; 2) prazosin, 25 microg/kg; 3) the nitric oxide synthase (NOS) inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), 5 mg/kg; or 4) the specific inhibitor of neuronal NOS, 7-nitroindazole (7-NI), 45 mg/kg. Arterial pressure and heart rate (HR) were continuously monitored. Microinjection of ANG-(1-7) or ANG II into the CVLM produced a significant decrease in mean arterial pressure (MAP; -11 +/- 1 mmHg, n = 12 and -10 +/- 1 mmHg, n = 10, respectively) that was not accompanied by consistent changes in HR or in cardiac output. The effect of ANG-(1-7) was abolished after treatment with methyl-atropine (-3 +/- 0.6 mmHg, n = 9) or L-NAME (-2.3 +/- 0.5 mmHg, n = 8) or 7-NI (-2.8 +/- 0.6 mmHg, n = 5). In contrast, these treatments did not significantly interfere with the ANG II effect (-10 +/- 2.6 mmHg, n = 8; -8 +/- 1.5 mmHg, n = 8; and -12 +/- 3.6 mmHg, n = 6; respectively). Peripheral treatment with prazosin abolished the hypotensive effect of ANG-(1-7) and ANG II. Microinjection of saline did not produce any significant change in MAP or in HR. These results suggest that the hypotensive effect produced by ANG II at the CVLM depends on changes in adrenergic vascular tonus and, more importantly, the hypotensive effect produced by ANG-(1-7) also involves a nitric oxide-related mechanism.
Alzamora
A C
AC
Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Santos
R A S
RA
Campagnole-Santos
M J
MJ
D018674:Adrenergic Antagonists / Q000494:pharmacology; D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002302:Cardiac Output / Q000187:drug effects; D018680:Cholinergic Antagonists / Q000494:pharmacology; D003864:Depression, Chemical; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology*; D008845:Microinjections; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology
D018674:Adrenergic Antagonists; D018680:Cholinergic Antagonists; D010446:Peptide Fragments; D000804:Angiotensin II; D000803:Angiotensin I; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; C118790:angiotensin I (1-7)