Pressure modulates the reactivity of isolated rabbit epicardial arteries.

1. The magnitude of responses to prostaglandin F2 alpha (PGF2 alpha) and adenosine (ADO) in pressurized rabbit epicardial coronary arteries (367 +/- 44 microns o.d.) with intact endothelium was assessed when they developed spontaneous tone. 2. The arteries were cannulated and changes in arterial diameter registered with an automated video perfusion system. The vessels, in the stabilization period at 60 mmHg, were divided into two groups, one exposed to a longitudinal stretch of +20% of unstretched initial length (Lo), and the other to +35% Lo, which developed spontaneous tone. In both cases, diameter-pressure curves were obtained by changing the intravascular pressure from 30 to 120 mmHg in aleatory steps of 30 mmHg (dp/dt = 15 mmHg s-1). 3. Diameter reduction of the arteries with stretch of +35% Lo in response to 1 microM PGF2 alpha was greater than that with stretch of +20% Lo. Likewise, increase of the arteries that had +35% Lo in response to 1 microM ADO was greater than with +20% Lo. 4. Intravascular flow (40 microliters min-1) increased the tone level of arteries. The addition of PGF2 alpha enhanced this tone which was similar to that obtained with a stretch of +35% Lo and no flow, whereas the effect of ADO was increased. 5. These data indicate that the vasomotor responses of PGF2 alpha and ADO are modulated by the degree of longitudinal stretch in epicardial arteries.

Alpha-adrenoceptors involved on the cardiovascular response induced by mianserin in the pithed rat.

1. The effects of the antidepressant drug mianserin on the cardiovascular responses induced by preganglionic electrical stimulation, and i.v. infusion of the adrenergic agonists noradrenaline (NA, alpha 1 and alpha 2), phenylephrine (alpha 1) and xylazine (alpha 2) in the pithed normotensive rat were studied. 2. Mianserin inhibited in a dose-dependent manner the pressor effect caused by electrical stimulation of spinal cord (Th7-Th9) and the infusion of NA, phenylephrine and xylazine. Cocaine increased the inhibitory effect of mianserin on the pressor effect caused by electrical stimulation and NA. 3. Mianserin blocked the xylazine-induced inhibition of cardiac nerve stimulation effect. 4. These results suggest that mianserin blocks the NA uptake, and it is more effective in blocking presynaptic alpha 2- than postsynaptic alpha-adrenoceptors.

Augmentation of endothelium-independent flow constriction in pial arteries at high intravascular pressures.

The effects of an increase in intraluminal pressure and flow on the diameter and active smooth muscle tone of pial arteries was studied in perfused segments. Resistance arteries (approximately 250-300 microns i.d.) were perfused under controlled pressure and flow conditions, and changes in arterial diameter registered with an automated video device. In any particular segment, diameter measurements were normalized to that observed at 5 mm Hg. Changes in active wall force were determined by relating the observed diameter under a particular set of conditions to the diameter at the same intramural pressure when smooth muscle tone was inhibited (calcium-free physiological saline solution) and to the diameter when smooth muscle cells were activated close to maximum (KCl; 89 mM). At 60 mm Hg, the diameter decrease of 21% in the absence of flow represented stretch-induced tone. No additional changes in diameter were encountered with a flow of 20 microliters/min. Diameter decreased a further 7% at 100 microliters/min. When intraluminal pressure was 90 mm Hg, diameter decreased 39% without flow. Additional constriction of 10% and 19% occurred at flows of 20 and 100 microliters/min, respectively. At the higher pressure, the vasoconstriction occasioned by flow was significantly greater than that at the lower pressure. After endothelium inactivation by passing hypo-osmotic Krebs' solution followed by air through the segment, mean diameter was less at each combination of pressure and flow, although this difference did not reach statistical significance. The diameter reductions to increases in pressure from 60 to 90 mm Hg and to flow at 40 microliters/min were not altered by endothelium inactivation.(ABSTRACT TRUNCATED AT 250 WORDS)

Flow-induced constriction and dilation of cerebral resistance arteries.

Rabbit pial resistance artery segments were cannulated at both ends so they could be perfused with physiological saline solution and were maintained in a tissue bath of the same solution. Both were kept at 37 degrees C and equilibrated with 95% O2 and 5% CO2. Perfusion pressure and flow were independently controlled by two servo-controlled pumps, and changes in the diameter of the segment were registered by an automated video technique. In the absence of flow, these segments maintained their diameter when intraluminal pressure was changed over the range 30-90 mm Hg. When intraluminal pressure was low (30 mm Hg), flow at 20 microliters/min caused dilation. This is half the rate of flow that causes a maximum flow-induced change under the conditions of these experiments. When pressure was high (90 mm Hg), the same flow rate caused constriction. Both responses usually continued as long as flow was maintained. Thus, flow-induced changes in the diameter of this artery can be initiated and are usually maintained despite the demonstrated capacity of the blood vessel wall to hold its diameter constant when pressure is changed in the absence of flow. The results suggest that these small arteries can independently respond to changes in pressure and flow and that the changes that occur in response to flow are not compensated for by changes in the myogenic response.

Resistance artery tone is influenced independently by pressure and by flow.

The responses of rabbit resistance arteries to pressure and flow have been examined using two in vitro techniques--when mounted isometrically in a myograph and when perfused using a video system that automatically registers diameter. The latter approach allows pressure and flow to be independently controlled. Under such circumstances three responses were studied; myogenic contraction and flow-dependent constriction and dilation. All responses occurred after endothelium removal and were unaffected by indomethacin (10(-60 M). The pressure and flow effects can be elicited separately and have different ionic bases. The effective stimulus for the myogenic response is stretch and that for flow is presumably shear stress. The mechano-transducers for these effects are different and are located either in the vascular smooth muscle cells or their surrounding extracellular matrix.

Effect of trazodone on oxidative metabolism of rat brain in vitro.

Oxygen uptake of rat brain homogenate was reduced by 1 mM trazodone, a new atypical antidepressant. Na,K-ATPase activity and the associated oxygen consumption of rat brain slices were also reduced. Oxygen consumption of rat brain slices was enhanced by dopamine and this effect was blocked by 0.0001 mM trazodone. This drug uncoupled oxidative phosphorylation.