Weakness of Sympathetic Neural Control of Human Pial Compared With Superficial Temporal Arteries Reflects Low Innervation Density and Poor Sympathetic Responsiveness

Abstract

Background and Purpose —The primary goal of these studies was to understand and investigate the capacity of perivascular nerves to influence the tone of human pial arteries and to compare them with other human cephalic arteries, the superficial temporal and middle meningeal. Methods —Responses to electrical activation of intramural nerves and related features of fresh segments of human cephalic arteries—the pial (PA; 478±34 μm ID), middle meningeal (MMA; 540±41 μm ID), and superficial temporal (STA; 639±49 μm ID)—obtained from patients aged 15 to 82 years during surgical procedures were studied on a resistance artery myograph. Results —The PA segment responses to electrical nerve activation and to norepinephrine (NE; 10 ⁻⁵ mol/L) were 1% and 21% of tissue maximum, respectively, compared with 6% and 34% for the MMA and 14% and 90% for the STA. Tissue maximum was defined as the force increase to 127 mmol/L KCl plus arginine vasopressin (1 μm). All arteries dilated well to acetylcholine. Possible explanations for the PA marginal neurogenic responses were assessed. NE ED ₅₀ was 5.4±2.2×10 ⁻⁷ mol/L and did not vary with age or diameter. NE responsiveness did not increase in vessels with spontaneous or raised potassium-induced tone. Relaxation to isoproterenol was variable and propranolol did not increase the neurogenic response. Neither N ^G -monomethyl- l -arginine, N ^G -nitro- l -arginine methyl ester, endothelium removal, nor indomethacin consistently influenced the contractions to NE or neurogenic reactivity. The weak PA neurogenic response is in keeping with its poor innervation. As determined by catecholamine histofluorescence, innervation in the PA is sparse, with density increasing in the order PA, MMA, and STA. The incidence of nerve structures in the PA adventitio-medial junction was only 3% of those in the STA, and these were situated more than 3 μm from the closest smooth muscle cell. Conclusions —We conclude that the weak neurogenic response of adult human pial artery reflects its poor innervation and responsiveness to NE, implying that these features are not important in the regulation of its diameter.