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 dosedependently 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.

Antinociceptive effect of intracerebroventricular administration of glycine transporter-2 inhibitor ALX1393 in rat models of inflammatory and neuropathic pain

“…Krowicki and Kapusta (2011) demonstrated that the microinjection of glycine into hypothalamic paraventricular nucleus caused a decrease in heart rate and diuretic and natriuretic responses that were abolished by strychnine. GlyT2 inhibitor in the hypothalamus might have cardiovascular and renal effects.…”

Direct Recording of Renal Sympathetic Nerve Activity in Unrestrained, Conscious Mice

“…These individual measurements were averaged for each portion of the experimental protocol to give a single value. Quantification of the experimental responses of RSNA was achieved by calculating the percent change of RSNA from baseline, which we designated as 100% 4 . Statistical analysis of the response of RSNA to sodium nitroprusside and phenylephrine was completed with Student's t-test; significance was accepted with p values below 0.05.…”

Altered Sedative Effects of Ethanol in Mice with α1 Glycine Receptor Subunits that are Insensitive to Gβγ Modulation

“…In the mature CNS, glycine activates mainly GlyRs composed of a1 and b subunits (Aguayo et al, 2004). Interestingly, Cl À -permeable GlyRs are one of the most sensitive ethanol molecular targets in the CNS, providing a neurobiological basis for its depressing effects on motor control, cardiovascular regulation, and sedation (Chang and Martin, 2011;Krowicki and Kapusta, 2011;Ren and Greer, 2006;Schmid et al, 1991). In addition, because recent studies showed that GlyRs are also found in supra spinal regions, such as VTA and nucleus accumbens, it is possible to postulate that they might be implicated in reward and ethanol-seeking behaviors (Chau et al, 2010;Li et al, 2012).…”