Pressure releases a transferable endothelial contractile factor in cat cerebral arteries.

Abstract

When exposed to an increasing transmural pressure, middle cerebral arteries of tbe cat exhibit reduction of internal diameter which is mediated by vascular muscle cell depolarization. This laboratory has recently demonstrated that this "pressure-induced" activation is dependent upon the presence of an intact endothelium. The present studies were undertaken to determine if this phenomenon is due to inhibition of tonically released endothelium-derived relaxing factors (EDRF) or release of a contractile substance. When cerebral arterial segments were pressurized to between 40 and 160 mm Hg there was 13.2% reduction in internal diameter accompanied by significant muscle cell depolarization from -53±2.7 to -22±1.4 mV. There was a significant positive correlation between the A E,, and step increases in transmural pressure. These excitatory responses were lost and vessels dilated to pressure when the endothelium was removed. Upon exposing the denuded vessel to a pressurized intact donor, the denuded vessel recovered its ability to contract and depolarize suggesting that a contractile substance might be released from the vascular endothelium upon pressurization. The EDRF antagonist oxyhemoglobin did not alter the excitatory response to pressure in these isolated cerebral arteries further suggesting that the reduction in diameter and muscle cell depolarization results from the release of a contractile substance from the vascular endothelium and not inhibition of EDRF. {Circulation Research 1989;65:193-198) R ecent reports have demonstrated that the vascular endothelium of various arterial beds may release factors that are contractile in nature. 1 -7 In the cerebral circulation, this apparent endothelium-dependent contraction is observed on elevation of transmural pressure and has been speculated to be partially responsible for blood flow autoregulation. 4 -8 One of the primary problems in defining a contractile factor thought to be released from the vascular endothelium is the ubiquitous presence of endothelium-derived relaxing factor(s) (EDRF). 9 -12 It is possible that the contractile response observed upon various maneuvers (e.g., hypoxia, pressure, and stretch) may be the result of inhibition of tonic release of EDRF. The present studies were designed to determine whether elevation of transmural pressure triggers endothelium-dependent contraction of cat cerebral arteries by effecting the synthesis and release of diffusible endothelial contractile factor(s) or, alternatively, by depressing the release of EDRF. The experiments were carried out using a novel bioassay system in which segments of intact and denuded cerebral arteries are pressurized and perfused in series.14 The results suggest that elevation of transmural pressure induces the release of a transferable contractile factor released from the endothelium that acts via muscle cell membrane depolarization. Materials and Methods GeneralAdult mongrel cats were anesthetized with sodium pentobarbital (60 mg/kg) and their brains removed. Middle cerebral art...

Endothelial dysfunction augments myogenic arteriolar constriction in hypertension.

“…Furthermore, the positive correlation between the increase in pressure and the additional constriction (Fig 1, middle) suggests that the synthesis of the endothelial factor or factors is coupled to the increases in pressure. Release of a constrictor factor from the endothelium in response to pressure 23 was reported previously in cerebral arteries of normotensive rats but as yet not in other vascular beds.…”

“…18 Although in most microvascular beds the myogenic response is intrinsic to vascular smooth muscle, 1719 -20 - 21 in some vessels the endothelium seems to have an obligatory role or contributes significantly to it. 22 - 23 Based on these studies we hypothesized (1) that the chronic presence of high intravascular pressure in hypertension may alter pres-sure-sensitive vascular mechanisms, resulting in an enhanced arteriolar tone and (2) that endothelial factors contribute to the enhanced pressure-induced constriction of arterioles.…”

High Intravascular Pressure Attenuates Vascular Dilation Responses of Small Mesenteric Arteries in the Rat

“…17,[20][21][22] Other possible explanations for our results include increased production of vasoconstrictor prostaglandins and/or endothelial contractile factors from vascular endothelial cells stimulated by elevated transmural pressure. [22][23][24] We also assessed the endothelium-independent dilation of SMA by using SNP: dilation responses to increasing doses of SNP were significantly reduced at high pressures and hence the sensitivity to SNP (ie, EC50) was also reduced. These results suggest that sustained high transmural pressure reduces the ability of vascular smooth muscle to dilate in response to nitro-vasodilators.…”

20-Hydroxyeicosatetraenoic acid is an endogenous vasoconstrictor of canine renal arcuate arteries.

“…The arteries were cut into small pieces and incubated with collagenase (500 units/ml), dithiothreitol (1 mg/ml), and soybean trypsin inhibitor (1 mg/ml) in a low calcium PSS containing (mM) NaCl 134, (1)(2)(3)(4)(5)(6)(7)(8)(9)(10) were formed between the pipette tip and the cell membranes by applying a light suction. When 145 mM KCI was used in the patch pipette and an intracellular potassium chloride concentration of 145 mM was assumed, the estimated resting membrane potential of the renal arterial muscle cells was approximately -55 to -60 mV (n=3), since no currents were recorded over this range.…”