Proceedings of The Physiological Society

University of Oxford (2011) Proc Physiol Soc 23, PC133

Poster Communications

Reduction in blood flow to a localized region of the dorsomedial medulla triggers hypertension in rats

J. Paton1, M. Bhuiyana2, S. Gouraud2, M. Takagishi2, A. Hatada2, A. Kohsaka2, M. Maeda2, H. Waki2

1. University of Bristol, Bristol, United Kingdom. 2. University of Wakayama, Wakayama, Japan.


Our hypothesis is that cerebral blood flow is a major long term determinant of the set point of arterial pressure. The brainstem nucleus of the solitary tract (NTS) is a pivotal region for regulating the set-point of arterial pressure (Doba & Reis, 19730; Duale et al. 2007), the mechanisms of which are not fully understood. Based on evidence that the NTS exhibits O2-sensing mechanisms (Lo et al. 2006), we examined whether a localized reduction of blood supply, resulting in stagnant hypoxia in the NTS, would lead to an increase in arterial pressure. Experiments were approved by the Ethics Committee for Animal Experiments at Wakayama Medical University, Japan. Male Wistar rats were anesthetized with urethane (1.45 g/kg i.p.) and the level of anaesthesia was monitored by assessing a limb withdrawal response to a noxious pinch. Supplements of urethane (0.145 g/kg, i.p.) were given as required. Cardiovascular parameters were measured before and after specific branches of superficial dorsal medullary veins were occluded using microclips at a level ±0.5 mm rostral/caudal to the calamus scriptorius; we assumed these were drainage vessels from the NTS and would produce stagnant hypoxia. Some rats were sino-aortic nerve denervated (SAD). Tissue blood flow was measured using a laser flow meter (Advance Co., Japan; 0.25 mm diameter) inserted into the dorsomedial medulla. Hypoxyprobe-1 - a marker for detecting cellular hypoxia in the post mortem tissue, confirm whether vessel occlusion induced hypoxia and if this included the NTS. Following vessel occlusion, blood flow in the dorsomedial medulla showed a ~60% decrease (resting level: mean±SEM, 49±4 ml/min/100g tissue; n=6, t-test p<0.001) and was associated with hypoxia in neurons located predominantly in the caudal and intermediate part of the NTS as revealed using hypoxyprobe-1 immunoreactivity. Vessel occlusion induced an immediate increase in arterial pressure in both intact (from 87±3 to 101±5 mmHg; n=9, P<0.05) and SAD rats (from 91±2 to 116±3 mmHg; n=11, P<0.05). The pressor response was greatest in SAD rats (P<0.01). In SAD rats this response persisted for >1 hour whereas in intact rats only 30 min. This study demonstrates that reduced blood flow and localized hypoxia in the NTS region increases a prompt rise in arterial pressure; the magnitude of the response is blunted by arterial baroreceptors. We suggest this response is a protective mechanism whereby the elevated systemic pressure is a compensatory reaction to enhance cerebral perfusion. Whether this mechanism has any relevance to the aetiology of neurogenic hypertension is unknown.

Where applicable, experiments conform with Society ethical requirements