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(Hypertension. 1998;31:328.)
© 1998 American Heart Association, Inc.

Scientific Contributions

Distinct Endothelial Impairment in Coronary Microvessels from Hypertensive Dahl Rats

Kathryn M. Gauthier-Rein; Nancy J. Rusch

From the Department of Physiology (K.M.G.-R., N.J.R.), Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226

Correspondence to: Nancy J. Rusch, PhD, Associate Professor, Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226. E-mail nrusch{at}mcw.edu

Hypertension has been linked to an impaired dilator function of the coronary microvascular endothelium in vivo. However, the profile and mechanism of this dysfunction remain obscure. Thus, this study compared diameter responses to acetylcholine (ACH), bradykinin (BKN), and substance P (SP) between coronary microvessels (i.d.=106±4 µm) dissected from left ventricles of normotensive and hypertensive Dahl rats (Dahl-NT and Dahl-HT, respectively). Vessels were cannulated and pressurized on glass pipettes at 80 mm Hg, and internal diameters were monitored by videomicroscopy. Coronary microvessels from Dahl-NT and Dahl-HT showed similar dilator responses to ACH (100 pmol/L to 10 µmol/L), with maximal diameter increases of 63±5 µm and 63±7 µm, respectively (n=31,17). However, only vessels from Dahl-NT showed dilator responses to SP (10 fmol/L to 1 nmol/L) and BKN (100 fmol/L to 10 nmol/L). All dilator responses persisted after N-nitro-L-arginine (10 µmol/L) or indomethacin (10 µmol/L), but were blunted after inhibition of cytochrome P450 by 10 µmol/L octadecynoic acid (n=6–8). These results suggest that: (1) coronary microvessels from Dahl-HT show a unique pattern of endothelial impairment, whereby ACH-induced relaxations persist at a time when dilator responses to SP and BKN are severely blunted, and (2) a cytochrome P450 product, rather than nitric oxide or prostacyclin, may partly mediate the vasodilator responses to ACH, SP and BKN.

Key Words: endothelium • hypertension • coronary arteries • vascular smooth muscle • cytochrome P450 • nitric oxide • cyclooxygenase

Abbreviations: ACH = acetylcholine • BKN = bradykinin • Dahl-HT = hypertensive Dalt rats • Dahl-NT = normotensive Dahl rats • INDO = indomethacin • L-NNA = N-nitro-L-arginine • ODYA = octadecynoic acid • SP = substance P

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