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NEUROHUMORAL CONTROL OF CIRCULATION AND HYPERTENSION

Y₁- and ₁-receptor control of basal hindlimb vascular tone

Neurovascular Research Laboratory, Faculty of Health Science, School of Kinesiology, The University of Western Ontario, London, Ontario, Canada N6A 3K7

Submitted 19 December 2003 ; accepted in final form 17 March 2004

The role of endogenous Y₁-receptor activation on skeletal muscle vasculature under baseline conditions is currently debated and no in vivo studies have been performed to address this issue. Therefore, this study was designed to address the effect of Y₁-receptor and/or ₁-adrenoceptor antagonism on basal hindlimb vascular conductance in male Sprague-Dawley rats in vivo. Left hindlimb vascular conductance, carotid artery mean arterial pressure, and heart rate were measured during low volume infusion of N²-(diphenylacetyl)-N-[(4-hydroxyphenyl)methyl]-D-arginine amide (BIBP3226; 100 µg/kg), prazosin (20 µg/kg), and combined blockade to the left hindlimb. Vascular conductance increased 1.5 ± 0.5 µl·min^–1·mmHg^–1 with BIBP3226 infusion, 1.7 ± 0.5 µl·min^–1·mmHg^–1 with prazosin infusion, and 4.8 ± 1.0 µl·min^–1·mmHg^–1 with combined blockade (P < 0.05). Interestingly, systolic vascular conductance increased in all three conditions, but diastolic vascular conductance only increased in the two conditions where BIBP3226 was present. These data indicate that Y₁-receptor activation plays an important role in the regulation of vascular conductance in the resting rat hindlimb. Furthermore, this effect was of the same magnitude as the ₁-adrenoceptor contribution. The differential flow profiles following ₁ blockade with and without Y₁-receptor blockade supports local differences in receptor distribution.

neuropeptide Y; norepinephrine; vascular conductance; BIBP3226

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