Angiotensin and baroreflex control of the circulation.
There is a close association between the location of angiotensin (Ang) receptors and many important brain nuclei involved in the regulation of the cardiovascular system. The present review encompasses the physiological role of Ang II in the brainstem, particularly in relation to its influence on baroreflex control of the heart and kidney. Activation of AT1 receptors in the brainstem by fourth ventricle (4V) administration to conscious rabbits or local administration of Ang II into the rostral ventrolateral medulla (RVLM) of anesthetized rabbits acutely increases renal sympathetic nerve activity (RSNA) and RSNA baroreflex responses. Administration of the Ang antagonist Sarile into the RVLM of anesthetized rabbits blocked the effects of Ang II on the RSNA baroreflex, indicating that the RVLM is the major site of sympathoexcitatory action of Ang II given into the cerebrospinal fluid surrounding the brainstem. However, in conscious animals, blockade of endogenous Ang receptors in the brainstem by the 4V AT1 receptor antagonist losartan resulted in sympathoexcitation, suggesting an overall greater activity of endogenous Ang II within the sympathoinhibitory pathways. However, the RSNA response to airjet stress in conscious rabbits was markedly attenuated. While we found no effect of acute central Ang on heart rate baroreflexes, chronic 4V infusion inhibited the baroreflex and chronic losartan increased baroreflex gain. Thus, brainstem Ang II acutely alters sympathetic responses to specific afferent inputs thus forming part of a potentially important mechanism for the integration of autonomic response patterns. The sympathoexcitatory AT1 receptors appear to be activated during stress, surgery and anesthesia.
Head
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Neuropharmacology Laboratory, Baker Medical Research Institute, Melbourne, Australia. Geoff.Head@baker.edu
Saigusa
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T
Mayorov
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D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001775:Blood Circulation / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology*; D007668:Kidney / Q000294:innervation; D019808:Losartan / Q000494:pharmacology; D008526:Medulla Oblongata; D011817:Rabbits; D051381:Rats; D044140:Receptor, Angiotensin, Type 1; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*
D057911:Angiotensin Receptor Antagonists; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D019808:Losartan