BACKGROUND: Recent evidence suggests that increases in cerebral vascular resistance may be important contributors to the aetiology and maintenance of hypertension. This may be mediated via the Cushing mechanism, i.e. an increase in systemic blood pressure evoked to compensate for decreased cerebral perfusion 1,2, but the mechanism remains elusive
HYPOTHESES: 1) the increased cerebrovascular resistance in the SHR is associated with alterations in the autonomic innervation of vertebrobasilar arteries prior to the onset of hypertension. 2) experimentally induced reduction in cerebral perfusion in the adult SHR leads to a further increase in systemic blood pressure (BP). 3). The mechanosensor, TRPV4, is critical for mediating the arterial pressure response to high cerebral artery resistance.
METHODS: Vessel peels of ventral brain vessels were IHC-labelled with α-DHB and α-VAChT fluorescent markers. BP was measured in adult SHRs subjected to3-vessel occlusion (3VO): right common carotid and bilateral vertebral artery occlusion and right carotid sinus denervation with or without osmotic pump infusion of ruthenium red (RR; to block TRV4 channels) into the right internal carotid. RESULTS: Parasympathetic innervation of brainstem vasculature in pre-hypertensive SHR was sparse andpersisted in adulthood. Reductions in sympathetic innervation (%) were observed in adult vs. pre-hypertensive SHRs. TRPV4 was observed on sympathetic fibres only. 3VO resulted in a short term increase in BP (SHR>Wistar) that was reduced after RR infusion and was followed by a sustained decrease in BP relative to control. Cerebral vessel arteriogenesis in response to 3VO was restricted in animals infused with RR.
CONCLUSIONS: The paucity of parasympathetic innervation of the vertebrobasilar circulation in SHR may impede vasodilatory responses.. The co-localisation of TRPV4 with sympathetic fibres may mediate part of the pressor response/re-modelling evoked by 3VO. TRPV4 may form part of a novel intra-cranial detection system guarding against cerebral hypoperfusion.