title: Pulse pressure-related changes in coronary flow in vivo are modulated by nitric oxide and adenosine.
abstract: Acute increases in arterial pulsatile load imposed on the left ventricle can increase coronary flow without commensurate changes in myocardial oxygen consumption. One explanation is that augmenting pulsatile perfusion at the same mean pressure itself stimulates flow by releasing endothelium-mediated vasorelaxant factors such as NO. The present study tested this hypothesis and determined whether NO and adenosine modulate this response. In open-chest anesthetized dogs, the distal left anterior descending coronary artery (LAD) was whole-blood-perfused by a novel servopump system to control mean and pulsatile perfusion pressure within the isolated vascular bed. Central aortic pressure was measured, stored to computer memory, and then digitally modified (varying the pulse pressure [PP]) to generate a real-time servocommand that was still synchronous with ventricular contraction. Left heart workload was unchanged. LAD flow was measured before and after increasing the PP (to 60 to 100 mm Hg) from baselines of either 0 or 40 mm Hg. With normal basal coronary vascular tone, raising the PP increased flow (+9 +/- 2% at a PP of 100 mm Hg). This response was markedly amplified (+39 +/- 8%) when basal tone was first partially reduced by adenosine. Competitive inhibition of NO synthase by N omega-monomethyl-L-arginine reduced acetylcholine and PP-dependent flow responses by 50%. Thus, enhanced pulsatile perfusion increases in vivo coronary flow in part by triggering NO release. The marked augmentation of the PP response with reduced basal coronary tone from adenosine suggests that this mechanism may play a role in improving myocardial perfusion during exercise.
authors.affiliation: Division of Cardiology, Johns Hopkins University, Baltimore, Md, USA.
authors.forename: F A
authors.initials: FA
authors.lastname: Recchia
authors.forename: H
authors.initials: H
authors.lastname: Senzaki
authors.forename: A
authors.initials: A
authors.lastname: Saeki
authors.forename: B J
authors.initials: BJ
authors.lastname: Byrne
authors.forename: D A
authors.initials: DA
authors.lastname: Kass
mesh_terms: D000241:Adenosine / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure; D003326:Coronary Circulation / Q000502:physiology*; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000241:Adenosine