Vascular Dysfunction in the Stroke Prone Spontaneously Hypertensive Rat Is Dependent on Constrictor Prostanoid Activity and Y Chromosome Lineage

Vascular dysfunction is a hallmark of hypertension and the strongest risk factor to-date for coronary artery disease. As Y chromosome lineage has emerged as one of the strongest genetic predictors of cardiovascular disease risk to-date, we investigated if Y chromosome lineage modulated this important facet in the stroke-prone spontaneously hypertensive rat (SHRSP) using consomic strains. Here we show that vascular dysfunction in the SHRSP is attributable to differential cyclo-oxygenase (COX) activity with NO levels playing a less significant role. Measurement of prostacyclin, the most abundant product of COX in the vasculature, confirmed augmented COX activity in the SHRSP aorta. This was accompanied by functional impairment of the vasodilatory prostacyclin (IP) receptor, while inhibition of the thromboxane (TP) receptor significantly ameliorated vascular dysfunction in the SHRSP, suggesting this is the downstream target responsible for constrictor prostanoid activity. Importantly, Y chromosome lineage was shown to modulate vascular function in the SHRSP through influencing COX activity, prostacyclin levels and IP dysfunction. Vascular dysfunction in the renal and intrarenal arteries were also found to be prostanoid and Y chromosome-dependent. Thus, in contrast to the widely-held view that COX inhibition is deleterious for the vasculature due to inhibition of the vasodilator prostacyclin, we show that COX inhibition abolishes vascular dysfunction in three distinct vascular be...

Source: Clinical Science - November 21, 2017 Category: Biomedical Science Authors: Khan, S. I., Andrews, K. L., Jefferis, A.-M., Jennings, G. L., Sampson, A. K., Chin-Dusting, J. P. F. Tags: PublishAheadOfPrint Source Type: research