Effect of chronic hypertension on cortical parenchymal arteriole tone and K+ mediated vasodilation

Abstract

Hypertension blunts functional hyperemia, a response in which increased neuronal activity causes local increases in cerebral blood flow. The mechanism mediating this occurrence is unknown. To test the hypothesis that increased vascular reactivity and altered vascular smooth muscle cell (VSMC) Ca2+ dynamics are involved in the blunted hyperemic response, we measured vascular responses and VSMC Ca2+in cortical parenchymal arterioles from normotensive (WKY) and hypertensive (SHR) rats. In the presence of the thromboxane agonist U46619 (150 nM), baseline tone and responses to the potent vasodilatory signal K+ (10 mM) were significantly higher in SHR vs. WKY (42.06% vs. 29.78%; P=0.0173 and 26.63% vs. 12.43%; P=0.0133 respectively). VSMC Ca2+ oscillation frequency induced by U46619 was significantly higher in SHR vs. WKY (0.1999Hz vs. 0.1493Hz; P=0.0007) whereas VSMC Ca2+ amplitude was not changed between groups. To conclude, both vascular tone and VSMC Ca2+ oscillation frequency are increased in SHR indicating that alterations in VSMC Ca2+dynamics likely contribute to increased parenchymal arteriole tone observed during hypertension. Further, responses to extracellular K+ are increased in SHR supporting previous data from our lab which demonstrates that the magnitude of dilatory responses is dependent on the degree of steady‐state baseline tone. AHA 11PRE7400037 to JAI; NIH 1R01HL089067‐01A2 to JAF.