Vertebrobasilar Remodeling In Hypertension: Cause or Consequence

Abstract

In 1961 Dickinson and Thomson observed that cerebral blood flow was diminished in hypertensive patients due to increased cerebrovascular resistance – primarily found in vertebrobasilar system that supplies the brainstem. We hypothesise that the hypoperfused brainstem results in hypertension and called it the “selfish brain” hypothesis. We found that the vertebrobasilar arteries of the spontaneously hypertensive rat (SHR) are hypertrophied/narrowed prior to the development of hypertension. They have increased mRNA levels of the angiotensin II receptor type 1a when compared to the Wistar Kyoto rats (74% increase for 5 weeks olds; 337% increase for 13 weeks olds). 10 day long treatment with angiotensin II (490 ng/kg/min) did not affect the morphology of the basilar artery in SHR. In SHR, we investigated whether sympathetic input from the superior cervical ganglia (SCG) to the vertebrobasilar arteries contributes to their re-modelling. Bilateral ganglionectomy (SCGx) transiently lowered systolic blood pressure (SBP; peak response at 11 days, 8±2 mmHg; P<0.05). Vessel morphology remained unchanged. Given that TRPV4 ion channels are implicated in remodelling of arteries we found elevated TRPV4 mRNA cerebral arteries in adult SHR compared to WKY rats (92% increase; P<0.05). Direct infusion of the TRPV4 agonist (GSK1016790A) into the internal carotid artery evoked vasodilatation of cerebral vessels and a dose dependent fall in SBP (peak response 24 hours 15% compared to a vehicle control; P<0.05). Thus, brainstem blood flow appears to play a role in the set-point generation of the arterial blood pressure. Our TRPV4 data may assist in the development of novel strategies to improve cerebral perfusion. Wellcome Trust and British Heart Foundation funded research.