Hypothalamic paraventricular nucleus mediates sodium-induced changes in cardiovascular and renal function in conscious sheep.
The contribution of the paraventricular nucleus of the hypothalamus (PVN) in mediating cardiovascular, renal, hormonal, and sympathetic nerve responses to increased cerebrospinal fluid (CSF) [Na(+)] was investigated in conscious sheep. Intracerebroventricular hypertonic NaCl (0.5 mol/l, 20 microl/min for 60 min) increased arterial blood pressure [AP; +13.4 (sd 2.0) mmHg, P < 0.001] and central venous pressure [CVP; +2.8 (sd 1.3) mmHg, P < 0.001], but did not significantly change heart rate or cardiac output (n = 6). Elevated CSF [Na(+)] also lowered plasma ANG II levels [-3.3 (sd 1.6) pmol/l, P = 0.004] and increased creatinine clearance [+31.5 (sd 32.7) ml/min, P = 0.03] and renal sodium excretion [+9.2 (sd 9.2) mmol/h, P = 0.003]. Lidocaine injection (1 microl, 2%) into the PVN prior to the ICV infusion had no apparent effect per se, but it abolished the AP, CVP, creatinine clearance, and ANG II responses to hypertonic NaCl, as well as reducing the increase in renal sodium excretion (n = 6). Subsequent studies were performed in conscious sheep with chronically implanted electrodes for measurement of renal sympathetic nerve activity (RSNA). The effects of ICV hypertonic NaCl on AP and RSNA were measured before and after PVN-injection of glycine (250 nmol in 500 nl artificial CSF). ICV NaCl increased AP and decreased RSNA (P < 0.001). These effects were significantly reduced by glycine (P = 0.02-0.001, n = 5). Saline injected into the PVN (n = 5) or lidocaine injected outside the PVN (n = 6) had no effect on the response to ICV hypertonic NaCl. These results indicate that the PVN is an important mediator of cerebrally induced homeostatic responses to elevated sodium concentration/hyperosmolality.
Frithiof
Robert
R
Karolinska Institutet, Dept. of Physiology and Pharmacology, S-17177, Stockholm, Sweden. robert.frithiof@ki.se
Ramchandra
Rohit
R
Hood
Sally
S
May
Clive
C
Rundgren
Mats
M
D000779:Anesthetics, Local / Q000008:administration & dosage; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D001794:Blood Pressure; D002302:Cardiac Output; D002496:Central Venous Pressure; D003243:Consciousness; D003404:Creatinine / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D005998:Glycine / Q000008:administration & dosage; D006339:Heart Rate; D006439:Hemodynamics / Q000187:drug effects; D006706:Homeostasis; D007263:Infusions, Parenteral; D007267:Injections; D007668:Kidney / Q000294:innervation*; D008012:Lidocaine / Q000008:administration & dosage; D009318:Natriuresis / Q000187:drug effects; D009994:Osmolar Concentration; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism*; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage / Q000378:metabolism*; D012756:Sheep; D012964:Sodium / Q000134:cerebrospinal fluid*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D014563:Urodynamics
D000779:Anesthetics, Local; D012462:Saline Solution, Hypertonic; D000804:Angiotensin II; D008012:Lidocaine; D012964:Sodium; D003404:Creatinine; D005998:Glycine