Blockade of angiotensin receptors in rat rostral ventrolateral medulla removes excitatory vasomotor tone.
The rostral ventrolateral medulla (RVLM) plays a primary role in the tonic and phasic control of arterial blood pressure. Stimulation of angiotensin receptors in this region appears to contribute to the tonic excitatory drive of RVLM neurons involved in the control of blood pressure, but the extent of this contribution has not been previously evaluated. The present study used bilateral microinjections of angiotensin receptor antagonists into the RVLM of chloralose-anesthetized rats to determine the degree to which tonic blood pressure was dependent upon this angiotensin-mediated input. Bilateral injection into the RVLM of 1 nmol of [Sar1, Thr8]angiotensin II or [Sar1, Ile8] angiotensin II decreased blood pressure approximately 40 mmHg. The decrease in blood pressure elicited by these angiotensin antagonists was nearly as great as that elicited by complete bilateral inhibition of the RVLM produced by local injections of muscimol or elicited by inhibition of the autonomic nervous system by intravenous injection of chlorisondamine. The decrease in blood pressure caused by injection of these angiotensin antagonists was localized to the RVLM and was dose related. Responses elicited by [Sar1, Thr8]angiotensin II were eliminated by coinjection of angiotensin. In addition to markedly decreasing resting blood pressure, 1 nmol of [Sar1, Thr8]angiotensin II injected into the RVLM, also completely antagonized the increase in blood pressure elicited by blocking the tonic inhibitory influence exerted on the RVLM by neurons in the caudal ventrolateral medulla. These results demonstrate that tonic stimulation of angiotensin receptors in the RVLM accounts for much of the excitatory sympathetic vasomotor drive emanating from the RVLM.
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Department of Neuroscience, University of Pittsburgh, Pennsylvania 15260, USA.
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D015059:1-Sarcosine-8-Isoleucine Angiotensin II / Q000494:pharmacology; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002714:Chlorisondamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism*; D008845:Microinjections; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014666:Vasomotor System / Q000502:physiology*
D057911:Angiotensin Receptor Antagonists; D000804:Angiotensin II; D009118:Muscimol; C014805:angiotensin II, Sar(1)-Thr(8)-; D015059:1-Sarcosine-8-Isoleucine Angiotensin II; D002714:Chlorisondamine