Intrathecal Kynurenate Decreases Arterial Pressure in Conscious DOCA‐Salt Hypertensive Rats

We have previously reported that blockade of spinal V1a receptors has no effect on the elevated mean arterial pressure (MAP) in DOCA‐salt hypertensive rats. These findings indicate that spinally released vasopressin does not contribute to maintenance of MAP during the established phase of DOCA‐salt hypertension. Anatomical and physiological evidence suggests that glutamate is another spinal neurotransmitter that may affect sympathetic nerve activity and MAP. Therefore, this study tested the hypothesis that glutamate acts in the spinal cord to maintain elevated MAP during DOCA‐salt hypertension. Rats were chronically instrumented with an indwelling catheter for intrathecal injections and a radiotelemeter to measure MAP. After four weeks of DOCA‐salt treatment, MAP was elevated in DOCA‐salt rats (140±7 mmHg) compared to sham‐treated controls (108±2 mmHg). Intrathecal (i.t.) injection of kynurenate (KYN; 500 nmol), a nonspecific glutamate receptor antagonist, caused marked reductions in MAP (−54±6 mmHg) and HR (−108±13 bpm) in DOCA‐salt rats. The MAP and HR responses to i.t. KYN were much less in sham‐treated controls (‐20±6 mmHg and ‐28±25 bpm, respectively). These results are consistent with the hypothesis that spinally released glutamate contributes to elevated MAP in DOCA‐salt rats. However, further studies are needed to definitively determine the site of action of i.t. KYN. Supported by HLR0164176.