Is tonic sympathetic vasoconstriction increased in the skeletal muscle vasculature of aged canines?

Abstract

We tested the hypothesis that tonic adrenergic and nonadrenergic receptor-mediated sympathetic vasoconstriction would increase at rest and during exercise with advancing age. Young (n = 6; 22 ± 1 mo; means ± SE) and old (n = 6; 118 ± 9 mo) beagles were studied. Selective antagonists for alpha-1, alpha-2, neuropeptide Y (NPY), and purinergic (P(2x)) receptors were infused at rest and during treadmill running at 2.5 mph and 4 mph with 2.5% grade. Prazosin produced similar increases in vascular conductance in young and old beagles at rest (Young: 158 ± 34%; Old: 98 ± 19%) and during exercise at 2.5 mph (Young: 80 ± 10%; Old: 58 ± 12%) and 4 mph and 2.5% grade (Young: 57 ± 5%; Old: 26 ± 4%). Rauwolscine caused similar (P > 0.05) increases in vascular conductance in old compared with young dogs at rest (Young: 119 ± 25%; Old: 64 ± 22%) and at 2.5 mph (Young: 86 ± 13%; Old: 60 ± 7%) and 4 mph with 2.5% grade (Young: 61 ± 5%; Old: 43 ± 7%). N2-(diphenylacetyl)-N-[4-hydroxyphenyl)methyl]-d-arginine amide (BIBP) caused a smaller increase (P < 0.05) in vascular conductance in old compared with young dogs at rest (Young: 179 ± 44%; Old: 91 ± 22%), whereas similar increases (P > 0.05) of experimental limb vascular conductance in young and old dogs occurred following BIBP during exercise at 2.5 mph (Young: 56 ± 16%; Old: 50 ± 12%) and 4 mph and 2.5% grade (Young: 45 ± 10%; Old: 25 ± 7%). Pyridoxal-phosphate-6-azophenyl-2'-4'-disulfonic acid infusion produced a larger increase in vascular conductance in old compared with young beagles at rest (Young: 88 ± 14%; Old: 191 ± 58%), whereas similar increases were observed at 2.5 mph (Young: 47 ± 18%; Old: 31 ± 11%) and 4 mph with 2.5% grade (Young: 26 ± 13%; Old: -18 ± 8%). At rest, NPY receptor-mediated restraint of skeletal muscle blood flow was reduced with advancing age, whereas P(2x) receptor-mediated restraint of skeletal muscle blood flow was increased. During exercise, the magnitude of adrenergic and nonadrenergic sympathetic vasoconstriction was not different between young and old dogs. Overall, these data demonstrate that adrenergic receptor-mediated vasoconstriction was not elevated at rest, but nonadrenergic sympathetic vasoconstriction was altered under basal conditions in aged beagles.

Fig. 1.

Percent change in experimental limb iliac vascular conductance in response to intra-arterial infusion of ACh (0.1 μg bolus) at rest in young (open bars) and old (solid bars) beagles. Values are expressed as means ± SE. **P < 0.001 indicates a significant difference between young and old.

Fig. 2.

Percent change in experimental limb iliac vascular conductance in response to intra-arterial infusion of the selective α1-adrenergic receptor antagonist prazosin (0.25 μg·ml⁻¹·min⁻¹) at rest and during treadmill running at 2.5 mph and 4 mph with 2.5% grade in young (open bars) and old (black bars) beagles. Absolute values for all hemodynamic variables prior to and following antagonist infusion are presented in Table 2. Values are expressed as means ± SE. ‡P < 0.001 indicates a main effect of exercise intensity.

Fig. 3.

Percent change in experimental limb iliac vascular conductance in response to intra-arterial infusion of the α2-adrenergic receptor antagonist rauwolscine (1.25 μg·ml⁻¹·min⁻¹) at rest and during treadmill running at 2.5 mph and 4 mph with 2.5% grade in young (open bars) and old (black bars) beagles. Absolute values for all hemodynamic variables prior to and following antagonist infusion are presented in Table 3. Values are expressed as means ± SE.

Fig. 4.

Percent change in experimental limb iliac vascular conductance in response to intra-arterial infusion of the selective NPY-Y1 receptor antagonist BIBP (2.5 mg bolus) at rest and during treadmill running at 2.5 mph and 4 mph with 2.5% grade in young (open bars) and old (black bars) beagles. Absolute values for all hemodynamic variables prior to and following antagonist infusion are presented in Table 4. Values are expressed as means ± SE. *P < 0.05 indicates a significant difference between young and old at rest. ‡P < 0.001 indicates a main effect of exercise intensity.

Fig. 5.

Percent change in experimental limb iliac vascular conductance in response to intra-arterial infusion of the purinergic receptor antagonist PPADS (40 mg bolus) at rest and during treadmill running at 2.5 mph and 4 mph with 2.5% grade in young (open bars) and old (black bars) beagles. Absolute values for all hemodynamic variables prior to and following antagonist infusion are presented in Table 5. Values are expressed as means ± SE. *P < 0.05 indicates a significant difference between young and old. ‡P < 0.001, indicates a main effect of exercise intensity.