NEUROGENIC VASOREACTIVE RESPONSE OF HUMAN INTERNAL THORACIC ARTERY SMOOTH-MUSCLE

The interaction between primary afferent neurons containing neuropepti des and the vascular smooth muscle is incompletely understood, To expl ore the function of perivascular afferent neurons and to determine whe ther they produce local effects on vascular smooth muscle cells, we in vestigated the effects of acute capsaicin and substance P administrati on in vitro on human internal thoracic arteries (ITA). Vessels were ob tained from patients undergoing coronary bypass or from multiorgan tra nsplant donors. Fourteen ITA segments (5 mm wide) were suspended as ri ngs between two stainless-steel stirrups in water-jacketed (37 degrees C) tissue baths under 2.5 to 3g of basal tension. The tissue baths co ntained 10 mL physiological salt solution (PSS) of the following compo sition (mM): NaCl, 119; KCl, 4.7; NaH2PO4, 1.0; MgCl2, 0.5; CaCl2, 2.5 ; NaHCO3, 25; and glucose, 11; aerated continuously with 95% O-2 and 5 % CO2. Peptidase inhibitors (phosphoramidon and captopril) were added to PSS to decrease peptide degradation, Mechanical responses were meas ured isometrically and recorded on a polygraph via isotonic force tran sducers. Vessels were preconstricted with submaximal concentrations of norepinephrine. After the tension had stabilized, substance P or caps aicin was added cumulatively to the tissue bath, At the end of the exp eriments, the viability of ITA was verified by its responses to endoth elial-dependent (acetylcholine) and endothelial-independent (sodium ni troprusside) vasodilators. In the endothelium-intact ITA segments, sub stance P produced relaxation of ITA smooth muscle while it induced sli ght contraction when the ITA was devoid of its endothelium (P = 0.0585 ). The addition of capsaicin to human ITA primarily produced contracti le effects on the developed smooth muscle force. The capsaicin-induced contraction of the ITA smooth muscle was independent of endothelial c ell integrity, although contraction was greater in the endothelium-int act ITA segments (P = 0.0165). The acute capsaicin exposure of human I TA revealed that primary afferent neurons containing neuropeptides inn ervate human ITAs. There is a real potential for perivascular afferent neurons and sensory peptides to influence the ITA smooth muscle funct ion. (C) 1997 Academic Press.