Skeletal muscle blood flow and O2 uptake during intravenous nicotine with and without hypertension.
The mechanism by which nicotine causes peripheral vasoconstriction and its relationship to the increased risk of peripheral vascular disease in smokers are unknown. To study the peripheral vascular effects of nicotine, we measured hemodynamic responses and oxygen consumption of the in situ gracilis muscle during intravenous (i.v.) nicotine infusions in anesthetized dogs. Nicotine 36.0 micrograms/kg/min increased gracilis artery pressure (Pga) 91 +/- 17% and muscle vascular resistance (MVR) 96 +/- 18% whereas muscle blood flow (MBF) and oxygen consumption (MVO2) were unchanged from baseline. In dogs with extracorporeal-controlled normotension during nicotine infusion, however, Pga was held at baseline levels but similar increases in MVR were observed (95 +/- 11%) as flows decreased 52 +/- 9%. Oxygen consumption decreased in direct proportion (53 +/- 5%) to MBF, indicating complete impairment of oxygen extraction (A-VO2). Thus impaired oxygen extraction was masked in dogs in which Pga was allowed to increase because of sustained pressure-dependent flows. Phenoxybenzamine block of muscle alpha-adrenoceptors increased MBF and MVO2 in both normotensive and hypertensive dogs. Combined alpha- and beta-blockade effectively neutralized all sympathoadrenal responses in the muscle. All the above results occurred regardless of innervation. Plasma levels of norepinephrine (NE) and epinephrine (EPI) increased greater than 1,000% during nicotine infusion. Apparently, these levels were high enough to (a) override dilator effects of plasma EPI and (b) cause vasoconstriction in muscle independent of nerve supply. Infusion of nicotine in the gracilis artery had no effect on muscle hemodynamics. Nicotine-induced increase in plasma catecholamines resulted in a powerful constriction of both resistance and oxygen-exchange vessels of skeletal muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
Rooney
M W
MW
Department of Anesthesiology, University of Illinois College of Medicine, Chicago.
Hirsch
L J
LJ
D000818:Animals; D004285:Dogs; D004837:Epinephrine / Q000097:blood; D006973:Hypertension / Q000503:physiopathology*; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D009132:Muscles / Q000098:blood supply* / Q000187:drug effects; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D009638:Norepinephrine / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects*; D010643:Phenoxybenzamine / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D010643:Phenoxybenzamine; D009538:Nicotine; D009638:Norepinephrine; D004837:Epinephrine