Cardiovascular responses elicited by a new endogenous angiotensin in the nucleus tractus solitarius of the rat

• Published in: American journal of physiology. Heart and circulatory physiology 2011-01, Vol.300 (1), p.H230-H240
• Main Authors: Chitravanshi, Vineet C, Sapru, Hreday N
• Format: Article
• Language: English
• Subjects: ACE inhibitors; Analysis of Variance; Angiotensin Receptor Antagonists - pharmacology; Angiotensinogen; Angiotensins - pharmacology; Angiotensins - physiology; Animals; Blood Pressure - drug effects; Blood Pressure - physiology; Cardiovascular Neurohormonal Regulation; Enzymes; Heart rate; Heart Rate - drug effects; Heart Rate - physiology; Imidazoles - pharmacology; Male; Microinjections; Naphthyridines - pharmacology; Neurons; Neurons - drug effects; Neurons - physiology; Peptide Fragments - pharmacology; Peptide Fragments - physiology; Pyridines - pharmacology; Rats; Rats, Wistar; Rodents; Solitary Nucleus - drug effects; Solitary Nucleus - physiology; Splanchnic Nerves - drug effects; Splanchnic Nerves - physiology; T cell receptors; Tetrazoles - pharmacology; Vagotomy
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00861.2010

Cardiovascular effects of angiotensin-(1-12) [ANG-(1-12)] were studied in the medial nucleus of the tractus solitarius (mNTS) in anesthetized, artificially ventilated, adult male Wistar rats. Microinjections (100 nl) of ANG-(1-12) (0.06 mM) into the mNTS elicited maximum decreases in mean arterial pressure (MAP; 34 ± 5.8 mmHg) and heart rate (HR; 39 ± 3.7 beats/min). Bilateral vagotomy abolished ANG-(1-12)-induced bradycardia. Efferent greater splanchnic nerve activity was decreased by microinjections of ANG-(1-12) into the mNTS. Blockade of ANG type 1 receptors (AT(1)Rs; using ZD-7155 or L-158,809), but not ANG type 2 receptors (AT(2)Rs; using PD-123319), significantly attenuated ANG-(1-12)-induced cardiovascular responses. Simultaneous inhibition of both angiotensin-converting enzyme (ACE; using captopril) and chymase (using chymostatin) completely blocked the effects of ANG-(1-12). Microinjections of A-779 [ANG-(1-7) antagonist] did not attenuate ANG-(1-12)-induced responses. Pressure ejection of ANG-(1-12) (0.06 mM, 2 nl) caused excitation of barosensitive mNTS neurons, which was blocked by prior application of the AT(1)R antagonist. ANG-(1-12)-induced excitation of mNTS neurons was also blocked by prior sequential applications of captopril and chymostatin. These results indicate that 1) microinjections of ANG-(1-12) into the mNTS elicited depressor and bradycardic responses by exciting barosensitive mNTS neurons; 2) the decreases in MAP and HR were mediated via sympathetic and vagus nerves, respectively; 3) AT(1)Rs, but not AT(2)Rs, mediated these actions of ANG-(1-12); 4) the responses were mediated via the conversion of ANG-(1-12) to ANG II and both ACE and chymase were involved in this conversion; and 5) ANG-(1-7) was not one of the metabolites of ANG-(1-12) in the mNTS.