Obesity is a risk factor for cardiovascular and metabolic disorders. The prevalence of obesity-associated hypertension has been rising globally, and it is mainly linked to the increasing consumption of processed as well as fast foods. The current trend indicates that women are more likely to become obese than men; however, the onset of hypertension is delayed in obese women until they reach postmenopausal age. Several reasons have been given for such disparity, such as reproductive hormones and distribution of body fat. In addition, obesity-induced hypertension is indicated in the overdrive of sympathetic nerves centrally and peripherally. For example, sympathetic denervation in the kidneys and celiac ganglionic blockade have demonstrated the role of sympathetic nerves in hypertension. Nevertheless, there is little knowledge regards to the effect of obesity on the underlying mechanisms in the sympathetic neurotransmission in the mesenteric blood vessels. Therefore, we tested the hypothesis that high fat diet (HFD) compared to control diet (CD) results in greater sympathetic neurotransmission and nerve distribution in the Dahl salt-sensitive (Dahl ss) rat. HFD fed rats gained more body weight than rats on CD, and males became more obese than females. Mean arterial pressure (MAP) was greater in HFD versus CD at 17- and 24-wk in both sexes. Nevertheless, males and females became equally hypertensive on both diets. In mesenteric artery (MA), neurogenic constriction was higher in HFD versus CD at 17-wk in males; however, this observation was not supported by changes in vascular reactivity or nerve density at the same time point. ATP is co-released with norepinephrine (NE) from the presynaptic nerves and it mediates purinergic neurotransmission. Moreover, the purinergic nerves were low in count at this time point indicating minimal contribution to the higher neurogenic response in HFD at 17-wk in males. In mesenteric vein (MV), neurogenic response was greater in HFD versus CD at 17-wk in males (similar to MA). There was also a greater adrenergic venous reactivity (norepinephrine mediated) and higher tyrosine hydroxylase (TH; sympathetic nerve marker) nerve density in HFD versus CD at 17-wk in males. This suggests HFD-induced hypertension is partly driven by adrenergic nerves from MV at 17-wk in males. Finally, HFD increased in most cases the sympathetic vesicles in the nerve cell bodies in celiac ganglion (CG), and sympathetic nerve fibers in MA and MV. In addition, three distinct populations of sympathetic vesicles/nerves were identified in CG, MA, and MV, namely TH-immunoreactive (TH-ir), vesicular nucleotide transporter (VNUT-ir; ATP marker), and TH/VNUT colocalization. The distribution of adrenergic, purinergic, and colocalized vesicles in cell bodies at the CG was not necessarily reflected in the periarterial and perivenous nerves. Taken together, HFD-associated hypertension is not driven by changes in the sympathetic neurotransmission from the mesenteric vasculature in male and female Dahl ss rats.
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