Effects of intrathecal kynurenate on arterial pressure during chronic osmotic stress in conscious rats

Abstract

Increased plasma osmolality elevates mean arterial pressure (MAP) through activation of the sympathetic nervous system, but the neurotransmitters released in the spinal cord to regulate MAP during osmotic stress remain unresolved. Glutamatergic neurons of the rostral ventrolateral medulla project to sympathetic preganglionic neurons in the spinal cord and are likely activated during conditions of osmotic stress; however, this has not been examined in conscious rats. This study investigated whether increased MAP during chronic osmotic stress depends on activation of spinal glutamate receptors. Rats were chronically instrumented with an indwelling intrathecal (i.t.) catheter for antagonist delivery to the spinal cord and a radiotelemetry transmitter for continuous monitoring of MAP and heart rate. Osmotic stress induced by 48 h of water deprivation (WD) increased MAP by ~15 mmHg. Intrathecal kynurenic acid, a nonspecific antagonist of ionotropic glutamate receptors, decreased MAP significantly more after 48 h of WD compared with the water-replete state. Water-deprived rats also showed a greater fall in MAP in response to i.t. 2-amino-5-phosphonovalerate. Finally, i.t. kynurenic acid also decreased MAP more in an osmotically driven model of neurogenic hypertension, the DOCA-salt rat, compared with normotensive controls. Our results suggest that spinally released glutamate mediates increased MAP during 48-h WD and DOCA-salt hypertension.

Roles of the subfornical organ and area postrema in arterial pressure increases induced by 48-h water deprivation in normal rats

“…The primary purpose of this study was to test the hypothesis that the SFO and/or the AP mediate the rise in arterial pressure induced by WD, using conscious rats instrumented for telemetric recordings of arterial pressure and heart rate. We confirm using telemetry (Veitenheimer and Osborn , ; Veitenheimer et al. ) that (1) WD elicits a gradual and progressive pressor response that is evident within 24 h and reaches a peak increment of ~15–20 mmHg after 48 h; (2) the rise in arterial pressure is accompanied by a transient bradycardia; and (3) both MAP and HR rapidly decrease when water is returned to the rats after 48 of WD.…”

“…In addition, total body sodium is reduced, due to both decreased food intake and also increased urinary sodium excretion, with subsequent hypovolemia. Despite these reductions in water and sodium, at least in rats, arterial pressure rises (Gardiner and Bennett 1985 ; Blair et al 1997 ; Scrogin et al 2002 ; Veitenheimer and Osborn 2011 , 2013 ; Veitenheimer et al 2012 . Three pressor pathways have been shown to contribute to this pressor response: angiotensin II, vasopressin, and the sympathetic nervous system (Gardiner and Bennett 1985 ; Scrogin et al 1999 , 2002 .…”

“…Water deprivation (WD) is associated not only with decreases in total body water but also in sodium secondary to a dehydration‐induced natriuresis (McKenna and Haines 1981 ; McKinley et al 1983 ; Thrasher et al 1984 . Yet, despite the resulting significant decrease in extracellular fluid volume, arterial pressure rises (Gardiner and Bennett 1985 ; Blair et al 1997 ; Scrogin et al 2002 ; Veitenheimer and Osborn 2011 , 2013 ; Veitenheimer et al 2012 . Previous work suggests that increased osmolality contributes to the hypertensive response via elevations in vasopressin and sympathetic nerve activity (Gardiner and Bennett 1985 ; Brooks et al 2005a .…”

The activation of the kynurenine pathway in a rat model with renovascular hypertension

“…In the work of Wang et al., 18 after microinjection of KYNA into the rostral ventrolateral medulla, a substantial drop in blood pressure values was observed. Likewise, Veitenheimer and Osborn 19 noticed decreased mean arterial pressure after intrathecal administration of KYNA. Moreover, derivative of AA (HMR1766) in intravenous bolus injection decreased arterial blood pressure in anesthetized pigs.…”