title: Microinjection of glycine into the hypothalamic paraventricular nucleus produces diuresis, natriuresis, and inhibition of central sympathetic outflow.
abstract: Strychnine-sensitive glycine receptors and glycine-immunoreactive fibers are expressed in the hypothalamic paraventricular nucleus (PVN), yet the functional significance of this innervation is unclear. Therefore, these studies examined the changes in cardiovascular and renal function and renal sympathetic nerve activity (RSNA) produced by the microinjection of glycine (5 and 50 nmol) into the PVN of conscious Sprague-Dawley rats. Microinjection of glycine into, but not outside of, the PVN dose-dependently increased urine flow rate and urinary sodium excretion and decreased RSNA. At the higher dose, PVN glycine also decreased heart rate; neither 5 nor 50 nmol PVN glycine altered mean arterial pressure. The glycine (50 nmol)-evoked diuresis and natriuresis were abolished in rats continuously infused intravenously with [Arg(8)]-vasopressin. Furthermore, chronic bilateral renal denervation prevented the bradycardia and diuresis to PVN glycine and blunted the natriuresis. In other studies, unilateral PVN pretreatment with the glycine receptor antagonist strychnine (1.6 nmol) prevented the effects of PVN glycine (50 nmol) on heart rate, RSNA, and renal excretory function. When microinjected bilaterally, PVN strychnine (1.6 nmol per site) evoked a significant increase in heart rate and RSNA without altering renal excretory function. These findings demonstrate that in conscious rats glycine acts in the PVN to enhance the renal excretion of water and sodium and decrease central sympathetic outflow to the heart and kidneys. Although endogenous PVN glycine inputs elicit a tonic control of heart rate and RSNA, the renal excretory responses to PVN glycine seem to be caused primarily by the inhibition of arginine vasopressin secretion.
authors.affiliation: Department of Pharmacology, Louisiana State University Health Sciences Center and MediProfile, Inc., New Orleans, LA 70118, USA. zbigniew.krowicki@mediprofileinc.com
authors.forename: Zbigniew K
authors.initials: ZK
authors.lastname: Krowicki
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Kapusta
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004231:Diuresis / Q000187:drug effects / Q000502:physiology*; D005998:Glycine / Q000008:administration & dosage*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D057967:Infusions, Intraventricular; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D008297:Male; D008845:Microinjections / Q000379:methods; D009318:Natriuresis / Q000187:drug effects / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017779:Sympathetic Fibers, Postganglionic / Q000187:drug effects / Q000502:physiology*
chemical_list: D005998:Glycine