Faculty Collaboration Database

Distinct endothelial impairment in coronary microvessels from hypertensive Dahl rats. Hypertension 1998 Jan;31(1 Pt 2):328-34

Date

02/07/1998

Pubmed ID

9453324

DOI

10.1161/01.hyp.31.1.328

Scopus ID

2-s2.0-0031611837 (requires institutional sign-in at Scopus site)   27 Citations

Abstract

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 microm) 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 micromol/L), with maximal diameter increases of 63+/-5 microm and 63+/-7 microm, 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 micromol/L) or indomethacin (10 micromol/L), but were blunted after inhibition of cytochrome P450 by 10 micromol/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.

Author List

Gauthier-Rein KM, Rusch NJ

MESH terms used to index this publication - Major topics in bold

Acetylcholine
Animals
Bradykinin
Coronary Vessels
Cytochrome P-450 Enzyme Inhibitors
Diet, Sodium-Restricted
Dose-Response Relationship, Drug
Endothelium, Vascular
Fatty Acids, Unsaturated
Hypertension
In Vitro Techniques
Indomethacin
Male
Microcirculation
Nitroarginine
Rats
Rats, Inbred Strains
Sodium, Dietary
Substance P
Vasodilation