Effects of Low Doses of Endothelin-1 on Basal Vascular Tone and Autoregulatory Vasodilation in Canine Coronary Microcirculation in Vivo

Abstract

ndothelin (ET)-1 is an endothelium-derived peptide that has a potent vasoconstrictor effect on a variety of vascular beds including the coronary microcirculation. [1][2][3][4] The plasma concentration of the peptide is increased in cardiovascular diseases such as essential hypertension, 5,6 vasospastic angina, 7 acute myocardial infarction, 8 and congestive heart failure. 9 Pretreatment with a monoclonal antibody against endothelin decreases the size of myocardial infarction in rat hearts. 10 The present authors 11 and other groups 12,13 have reported that the opening of ATP-sensitive potassium channels has a crucial role in the dilation of coronary resistance vessels during ischemia, hypoxemia, reactive hyperemia and autoregulation. We have also reported that pertussis toxin (PTX)-sensitive G protein mediates autoregulation and ischemic dilation in the canine coronary microcirculation. 14 On the other hand, ET-1 has been reported to block ATPsensitive potassium channels in cultured smooth muscle cells of the porcine coronary artery. 15 ET-1 also reversibly inhibits ATP-sensitive potassium channels of rat cardiac myocytes via an effect on PTX-sensitive G protein coupled to ET receptors. 16 Therefore, it is possible that a threshold concentration of ET-1 increases the vulnerability of hearts Japanese Circulation Journal Vol.63, August 1999 to myocardial ischemia by increasing the basal tone of coronary vessels or by attenuating the physiological responses such as autoregulation during the reduction in perfusion pressure. Accordingly, we assessed the effect of low doses of ET-1 on the vascular tone and on the physiological responses of coronary microvessels during a reduction in the coronary perfusion pressure. Methods General PreparationTwenty-four small mongrel dogs of either sex, weighing 5.8-9.9 kg, were premedicated with ketamine (10 mg/kg, im) and then anesthetized with an intravenous injection of -chloralose (60 mg/kg, Wako Chemicals). Additional doses, when necessary, were given to maintain anesthesia. The animals were intubated and mechanically ventilated (Model NSH-34RH, Harvard Apparatus, South Natic, MS, USA) at an end expiratory pressure of 3-5 cm H2O. Metabolic acidosis during the experiments was prevented by intravenous infusion of sodium bicarbonate. Arterial blood gases were maintained within the physiological range by adjusting the rate and volume of a ventilator and/or by using oxygen-enriched air. Body temperature was maintained at 37-38°C by means of a homeo-thermic blanket system. A catheter was introduced into the right external jugular vein for the infusion of drugs and fluid. Aortic pressure was measured at the aortic root with a catheter passed through the right carotid artery and Jpn Circ J 1999; 63: 617 -623 (Received April 15, 1999; accepted May 17, 1999 The plasma level of endothelin-1 (ET-1) increases in several cardiovascular disorders. The present study examined whether threshold doses of ET-1 affect vascular tone and autoregulatory vasodilation during a reduction in perfusion p...

Cold-acclimation leads to differential regulation of the steelhead trout (Oncorhynchus mykiss) coronary microcirculation

“…In all isolated fish vessel studies to date, ET-1 is one of the most potent vasoconstrictors (78,88,96). Consistent with that described for similar-sized mammalian coronary microvessels (105) and isolated trout coronary artery rings (78), the constrictor effect of ET-1 on the trout coronary arterioles was long lasting and sustained. Interestingly, ET-1-mediated vasoconstriction of isolated trout coronary microvessels was only initiated once nanomolar concentrations were reached (ϳ7% change from resting ID at 10 Ϫ9 M) suggesting that, similar to mammals, the role of ET-1 in the regulation of vascular resistance is likely that of a paracrine or autocrine mediator versus a circulating hormone (61).…”

Evaluation of Arteriolar Hyalinosis of the Skin of Patients With Chronic Congestive Heart Failure.

“…[4][5][6] Skin samples from the thigh were used in this study because of the convenience in sampling at the time of cardiac catheterization. 7 The skin of the patients with peripheral edema of non-cardiac origin was not examined, but the sampling and processing techniques for the control subjects and patients were similar, and thus the difference between the 2 groups appears to be real.…”

Regulation of coronary vascular tone via redox modulation in the α1-adrenergic-angiotensin-endothelin axis of the myocardium

“…These results suggest that ␣ 1-adrenergic stimulation in cardiac myocytes produces angiotensin I and H 2O2 and that angiotensin releases ET-1 through NADPH oxidase in coronary arterioles. Thus, coronary vasoconstriction via the ␣-adrenergic-angiotensin-ET axis appears to require redox-mediated signaling in cardiac and vascular cells.␣ 1-adrenoceptor; coronary vasomotion; reactive oxygen species ENDOTHELIN (ET) is an endogenous factor that produces robust and long-lasting coronary vasoconstriction (8,9,28). Therefore, it is imperative that the release and/or production of ET by coronary and myocardial cells are carefully regulated.…”