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

Abstract

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.

• Authors: Vineet C Chitravanshi, Hreday N Sapru
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 300 Issue 1 Pg. H230-40 (Jan 2011) ISSN: 1522-1539 [Electronic] United States
• PMID: 21076017 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Angiotensin Receptor Antagonists
• Angiotensins
• Imidazoles
• Naphthyridines
• Peptide Fragments
• Pyridines
• Tetrazoles
• ZD 7155
• proangiotensin-12, rat
• Angiotensinogen
• PD 123319
• L 158809

Topics

• Analysis of Variance
• Angiotensin Receptor Antagonists (pharmacology)
• Angiotensinogen
• Angiotensins (pharmacology, physiology)
• Animals
• Blood Pressure (drug effects, physiology)
• Heart Rate (drug effects, physiology)
• Imidazoles (pharmacology)
• Male
• Microinjections
• Naphthyridines (pharmacology)
• Neurons (drug effects, physiology)
• Peptide Fragments (pharmacology, physiology)
• Pyridines (pharmacology)
• Rats
• Rats, Wistar
• Solitary Nucleus (drug effects, physiology)
• Splanchnic Nerves (drug effects, physiology)
• Tetrazoles (pharmacology)
• Vagotomy