Characteristics of canine coronary resistance arteries: importance of endothelium

Abstract

Canine coronary resistance vessels were studied in vitro to examine the role of the endothelium in modulating responses to acetylcholine, vasopressin, and thrombin and to compare these responses to those found in large epicardial vessels. Acetylcholine had no effect on passively distended microvessels; however, after preconstriction with the thromboxane analogue, U 46619 caused dose-dependent vasodilation [50% effective concentration (EC50), 0.05 microM; maximum response, 97.9 +/- 2.1% relaxation]. Large epicardial arterial rings studied in organ chambers similarly relaxed to acetylcholine (EC50, 0.07 microM; maximum response, 79 +/- 5% relaxation). Hemoglobin was utilized to inactivate endothelium-derived relaxing factor (EDRF), resulting in reversal of acetylcholine vasodilation in both the microvessels (92 +/- 3.2% reversal) and the large epicardial vessels (117 +/- 9%). Hemoglobin had no effect on passively distended or preconstricted microvessels. Vasopressin constricted resistance vessels by 22.3 +/- 5.9 microns at 500 microU/ml. Hemoglobin potentiated this response by 100%, suggesting that vasopressin elicited EDRF release. In large coronary arteries, however, vasopressin elicited endothelium-dependent dilation with maximal relaxation of 36 +/- 9% at 3,000 microU/ml. Thrombin produced endothelium-dependent relaxation of large epicardial arterial rings but only constricted coronary microvessels. The response to thrombin was not altered by hemoglobin. This study demonstrates that the endothelium of coronary microvessels, like that of larger vessels, importantly modulates vascular reactivity to selected agents. Furthermore, major differences exist between large and small coronary arteries in their response to vasopressin and thrombin.

Impact of PercuSurge Device Conjugative With Intracoronary Administration of Nitroprusside on No-Reflow Phenomenon Following Primary Percutaneous Coronary Intervention

“…28 Additionally, although NTG is an effective vasodilator for large epicardial vessels, it is significantly less effective in the microvascular circulation. 28 On the other hand, NO, which is derived from NTP without the requirement for prior intracellular metabolism, 21 is a potent vasodilator in the resistance arteriolar circulation 19,29 and plays a significant role in controlling blood flow through the coronary microcirculation. 20,29 Furthermore, NO could positively affect latent collaterals or collateral blood flow by eliciting vasodilatation or inhibiting platelet aggregation in the vascular bed distal to the target lesion.…”

“…20,29 Furthermore, NO could positively affect latent collaterals or collateral blood flow by eliciting vasodilatation or inhibiting platelet aggregation in the vascular bed distal to the target lesion. 22,30 These mechanisms 15,16,[19][20][21][22][28][29][30] can explain why NTP was more effective than NTG in improving the final angiographic results. Second, recent studies have demonstrated that HBTF 4 and lipid pool-like content 31 in large IRAs are predictors of slow-flow or no-reflow, because distal macro-and microembolism of thrombi and plaque material frequently occurs in these vessels during balloon dilatation or stenting, which, in turn, induces severe microvascular dysfunction.…”

Endothelium-mediated coronary blood flow modulation in humans. Effects of age, atherosclerosis, hypercholesterolemia, and hypertension.

“…This controversy stems from experimental in vitro studies, which failed to demonstrate endothelium-dependent relaxations to acetylcholine in ring preparations of microvessels (30,31). However, when the microvascular effects of acetylcholine were investigated in pressurized arteries exposed to flow, which much more closely resembles the in vivo situation, it could be demonstrated that acetylcholine produces vascular relaxation by the release of EDRF also in the resistance vasculature ofall species examined this far (21,22,(32)(33)(34). Importantly, when methylene blue, an inhibitor of soluble guanylate cyclase, is infused into the human coronary circulation in vivo, the dilator effects of acetylcholine upon coronary microvessels are reversed to constrictor effects with dramatical increases in coronary vascular resistance (35).…”

Selective Intracoronary Administration of Nitroprusside Before Balloon Dilatation Prevents Slow Reflow During Percutaneous Coronary Intervention in Patients With Acute Myocardial Infarction

“…[7][8][9] Nitric oxide is a potent vasodilator in the resistance arteriolar circulation and plays a significant role in coronary blood flow through the microcirculation. 10,11) In patients with slow or no reflow, nitroglycerin used to be injected into the coronary artery. To derive nitric oxide, nitroglycerin has to be metabolized by the vascular wall.…”

“…10,11) Nitroprusside is a direct donor of nitric oxide. 12) It has been shown that intracoronary nitroprusside injection is a safe and effective technique for managing the slow reflow phenomenon once it occurs during coronary intervention.…”