Dissociation between sympathetic nerve traffic and sympathetically mediated vascular tone in normotensive human obesity

Abstract

Obesity increases the risk of hypertension and its cardiovascular complications. This has been partly attributed to increased sympathetic nerve activity, as assessed by microneurography and catecholamine assays. However, increased vasoconstriction in response to obesity-induced sympathoactivation has not been unequivocally demonstrated in obese subjects without hypertension. We evaluated sympathetic alpha-adrenergic vascular tone in the forearm by brachial arterial infusion of the alpha-adrenoreceptor antagonist phentolamine (120 microg/min) in normotensive obese (daytime ambulatory arterial pressure: 123+/-1/77+/-1 mm Hg; body mass index: 35+/-1 kg/m(2)) and lean (daytime ambulatory arterial pressure: 123+/-2/77+/-2 mm Hg; body mass index: 22+/-1 kg/m(2)) subjects (n=25 per group) matched by blood pressure, age, and gender. Microneurographic sympathetic nerve activity to skeletal muscle was significantly higher in obese subjects (30+/-3 versus 22+/-1 bursts per minute; P=0.02). Surprisingly, complete alpha-adrenergic receptor blockade by phentolamine (at concentrations sufficient to completely inhibit norepinephrine and phenylephrine-induced vasoconstriction) caused equivalent vasodilatation in obese (-57+/-2%) and lean subjects (-57+/-3%; P=0.9). In conclusion, sympathetic vascular tone in the forearm circulation is not increased in obese normotensive subjects despite increased sympathetic outflow. Vasodilator factors or mechanisms occurring in obese normotensive subjects could oppose the vasoconstrictor actions of increased sympathoactivation. Our findings may help to explain why some obese subjects are protected from the development of hypertension.

Figure 1

Relation between arm and leg mSNA in obese (circle) and lean (triangle) female (closed) and male (open) subjects.

Figure 2

A, left, Similar forearm vasoconstriction to norepinephrine 48 and 480 pmol/min is depicted for obese (●) and lean (△) normotensive subjects. Right, forearm vascular responses to norepinephrine 480 pmol/min infused alone and coinfused with phentolamine 120 µg/min are depicted for obese (■) and lean (□) subjects. The absence of vasoconstriction to norepinephrine/phentolamine coinfusion confirms that α-adrenoreceptor blockade was maximal at the phentolamine dose of 120 µg/min. In fact, vasodilatation was observed presumably because of the β-adrenoreceptor effect of norepinephrine. NE indicates norepinephrine; Phen, phentolamine. Data are means ± SEMs. B, left, Similar forearm vasoconstriction to phenylephrine 0.08 and 1.29 µg/min is depicted for obese (●) and lean (△) subjects. Right, forearm vascular responses to phenylephrine 1.29 µg/min infused alone and coinfused with phentolamine 194 µg/min is depicted for obese (■) and lean (□) subjects. The absence of vasoconstriction to phenylephrine/ phentolamine coinfusion confirms that α-adrenoreceptor blockade was maximal at the phentolamine dose of 194 µg/min. PE indicates phenylephrine; Phen, phentolamine. Data are means ± SEMs.

Figure 3

A, Similar forearm vasodilatation to 12 and 120 µg/min of phentolamine infusion is depicted for obese (●) and lean (△) normotensive subjects. Data are means ± SEM. B, Similar forearm vasodilatation to 120 and 194 µg/min of phentolamine infusion is depicted for obese (●) and lean (△) normotensive subjects. Data are means ± SEMs.

Figure 4

Similar vasodilatation to equal intra-arterial doses of phentolamine (194 µg/min in obese vs 120 µg/min in lean) is depicted in obese (■) and lean (□) subjects. A 100% α-adrenergic blockade was achieved with a 120-µg/min phentolamine dose in all of the groups, because an increase in dose by 1.6-fold did not lead to any increase in vasodilatation. Data are means ± SEMs.