Sodium intake influences hemodynamic and neural responses to angiotensin receptor blockade in rostral ventrolateral medulla.
To determine the effects of physiological alterations in endogenous angiotensin II activity on basal renal sympathetic nerve activity (RSNA) and its arterial baroreflex regulation, angiotensin II type 1 receptor antagonists were microinjected into the rostral ventrolateral medulla of anesthetized rats consuming a low, normal, or high sodium diet that were instrumented for simultaneous measurement of arterial pressure and RSNA. Plasma renin activity was increased in rats fed a low sodium diet and decreased in those fed a high sodium diet. Losartan (50, 100, and 200 pmol) decreased heart rate and RSNA (but not mean arterial pressure) dose-dependently; the responses were significantly greater in rats fed a low sodium diet than in those fed a high sodium diet. Candesartan (1, 2, and 10 pmol) decreased mean arterial pressure, heart rate, and RSNA dose-dependently; the responses were significantly greater in rats fed a low sodium diet than in those fed a normal or high sodium diet. [D-Ala(7)]Angiotensin-(1-7) (100, 200, and 1000 pmol) did not affect mean arterial pressure, heart rate, or RSNA in rats fed either a low or a high sodium diet. In rats fed a low sodium diet, candesartan reset the arterial baroreflex control of RSNA to a lower level of arterial pressure, and in rats with congestive heart failure, candesartan increased the arterial baroreflex gain of RSNA. Physiological alterations in the endogenous activity of the renin-angiotensin system influence the bradycardic, vasodepressor, and renal sympathoinhibitory responses to rostral ventrolateral medulla injection of antagonists to angiotensin II type 1 receptors but not to angiotensin-(1-7) receptors.
DiBona
G F
GF
Department of Internal Medicine, University of Iowa College of Medicine, and Veterans Administration Medical Center, Iowa City, Iowa 52242, USA.
Jones
S Y
SY
D000803:Angiotensin I / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D017704:Baroreflex / Q000502:physiology*; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006333:Heart Failure / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007668:Kidney / Q000294:innervation* / Q000502:physiology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects; D008845:Microinjections; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000378:metabolism*; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000502:physiology; D012982:Sodium, Dietary / Q000008:administration & dosage*; D013564:Sympathetic Nervous System / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D010446:Peptide Fragments; D011945:Receptors, Angiotensin; D012982:Sodium, Dietary; D013777:Tetrazoles; D000803:Angiotensin I; D012083:Renin; C118790:angiotensin I (1-7); D019808:Losartan; C081643:candesartan