Augmented vasoconstrictor response to changes in vascular transmural pressure in patients with essential arterial hypertension

The vasoconstrictor response to increase in venous transmural pressure in subcutaneous tissue was studied in 9 patients with essential arterial hypertension. Subcutaneous blood flow was measured on the distal part of the forearm and at the lateral malleolus by the local ¹³³Xe washout technique. Increase in venous transmural pressure was obtained by lowering the area under study 40cm below midaxillary line in the recumbent subject. Average mean arterial pressure ± 1 S.E. was 133 ± 6 mmHg. The fractional increase in vascular resistance induced by arteriolar constriction was more pronounced in the hypertensive patients than in a normotensive control group. “Minimal vascular resistance” in the papaverine relaxed vascular bed was higher in the hypertensive patients than in the controls. Distensibility of the papaverine relaxed resistance vessels was diminished in the patients. Follow-up studies after 6–18 months of anti-hypertensive treatment indicate that the vasoconstrictor response as well as “minimal vascular resistance” are normalized, whereas the distensibility of the papaverine relaxed arterioles remained unaltered in the hypertensive patients. The results indicate that the arteriolar smooth muscle cells of hypertensive patients are subjected to reversible hypertrophy whereas the reduced distensibility of the resistance vessels is due to irreversible structural changes.     

Metabolic control of large-bore arterial resistance vessels,arterioles, and veins in cat skeletal muscle during exercise

The metabolic control of the vascular bed in cat gastrocnemius muscle during exercise was studied with a new technique (Björnberg et al. 1988) permitting continuous and simultaneous recordings of arteriolar and capillary pressures, and of resistances in the following consecutive vascular section: proximal arterial resistance vessels > 25 μm, arterioles < 25 μm, and on the venous side. The study thereby provided quantitative data for resistance and active intrinsic tone in these vascular segments at rest, during graded exercise vasodilatation, and in the post-exercise period. Slight activation of the metabolic control system by low-frequency somatomotor nerve stimulation (light exercise') caused inhibition of intrinsic tone and decreased vascular resistance selectively in the arteriolar section. At increasing workloads, arteriolar resistance was further decreased, but resistance and tone in the proximal arterial resistance vessels and the veins then became clearly reduced as well. This difference in effectiveness of the metabolic control system on the different segments of the vascular bed was expressed quantitatively in terms of a ‘metabolic vasodilator index’. Graded activation of the metabolic control system led to a marked segmental redistribution of intrinsic vascular tone, in turn resulting in an increased pressure drop across the proximal arterial vessels and the veins and a decreased pressure drop over the arterioles. The observed decrease in the pre- to post-capillary resistance ratio caused, at a constant arterial pressure of 100 mmHg, a graded increase in capillary pressure with increasing workloads, at maximum vasodilatation by an average value of 14 mmHg above the resting control value of 15.4 ± 0.6 mmHg. In the post-exercise period, recovery of vascular tone to control was more rapid in the proximal arterial resistance vessels and the veins than in the arteriolar segment.     

Sympathetic alpha-adrenergic control of large-bore arterial vessels, arterioles and veins, and of capillary pressure and fluid exchange in whole-organ cat skeletal muscle

The sympathetic nervous control of the vascular bed of cat gastrocnemius muscle was studied with a new whole-organ technique which permits simultaneous, continuous and quantitative measurements of capillary pressure (Pc), capillary fluid exchange and resistance reactions in the whole vascular bed and in its three consecutive sections: large-bore arterial vessels (greater than 25 microns), arterioles (less than 25 microns) and veins. The results demonstrated a distinct neural control of all three consecutive vascular sections, graded in relation to the rate of nerve excitation up to maximum at 16 Hz. Stimulation at high rates, which in the steady state caused an average rise of overall regional resistance from 15.3 to 120 PRU (7.8-fold increase), thus raised large-bore arterial vessel resistance from 8.8 to 64 PRU (7.3-fold increase), arteriolar resistance from 4.5 to 49 PRU (10.9-fold increase) and venous resistance from 2.0 to 7 PRU (3.5-fold increase). The rate of resistance development (PRUs-1) of the sympathetic constrictor response was much higher in the arteriolar than in the other sections, which indicates that the neural control is especially prompt and efficient in the arterioles. A passive component was shown to contribute to the described responses only on the venous side, but in no case by more than 10% of the total sympathetic venous resistance response, which thus is mainly active. Of special functional importance was that the new technique provided information about the adrenergic control of Pc in absolute figures. From the control value of 19 mmHg, graded sympathetic stimulation caused a graded decline in Pc, at maximum constriction by about 7 mmHg. This resulted in marked net transcapillary fluid absorption, in turn increasing plasma volume.     

Sympathetic a-adrenergic control of large-bore arterial vessels,arterioles and veins,and of capillary pressure and fluid exchange in whole-organ cat skeletal muscle

The sympathetic nervous control of the vascular bed of cat gastrocnemius muscle was studied with a new whole-organ technique which permits simultaneous, continuous and quantitative measurements of capillary pressure (P_c), capillary fluid exchange and resistance reactions in the whole vascular bed and in its three consecutive sections: large-bore arterial vessels (> 25 μm), arterioles (< 25 μm) and veins. The results demonstrated a distinct neural control of all three consecutive vascular sections, graded in relation to the rate of nerve excitation up to maximum at 16 Hz. Stimulation at high rates, which in the steady state caused an average rise of overall regional resistance from 15.3 to 120 PRU (7.8-fold increase), thus raised large-bore arterial vessel resistance from 8.8 to 64 PRU (7.3-fold increase), arteriolar resistance from 4.5 to 49 PRU (10.9-fold increase) and venous resistance from 2.0 to 7 PRU (3.5-fold increase). The rate of resistance development (PRU s^-1) of the sympathetic constrictor response was much higher in the arteriolar than in the other sections, which indicates that the neural control is especially prompt and efficient in the arterioles. A passive component was shown to contribute to the described responses only on the venous side, but in no case by more than 10% of the total sympathetic venous resistance response, which thus is mainly active. Of special functional importance was that the new technique provided information about the adrenergic control of P_c, in absolute figures. From the control value of 19 mmHg, graded sympathetic stimulation caused a graded decline in P_c, at maximum constriction by about 7 mmHg. This resulted in marked net transcapillary fluid absorption, in turn increasing plasma volume.     

Constrictor response of small pulmonary arteries to acute pulmonary hypertension during left atrial pressure elevation

Acute elevations in left atrial pressure (LAP) were induced by altering the volume of air within a balloon inserted into the left atrium; the changes in internal diameter (ID) of small muscular pulmonary arteries (100-600 microns ID) in response to the associated rises of pulmonary arterial pressure (PAP) were measured using an X-ray TV system on the in vivo cat lung. When LAP was elevated to 14 +/- 1, 24 +/- 1, and 30 +/- 1 mmHg, PAP was increased to 21 +/- 1, 30 +/- 1, and 37 +/- 1 mmHg, respectively. With PAP ranging from 16 (control value) to 21 mmHg the ID did not dilate significantly. With PAP of 30-37 mmHg significant ID dilation occurred. The magnitude of the ID dilation (16%) with PAP of 37 mmHg, however, was significantly smaller than that (20%) with PAP of 30 mmHg despite the greater pressure rise. When the elevated PAP of 30-37 mmHg was quickly returned to the control level by rapid balloon deflation, the ID constricted significantly below the control level. The magnitude of the ID constriction was proportional to the degree of the preceding PAP rise and was maximal in the arteries of 200-400 microns ID. A papaverine hydrochloride injection combined with the balloon deflation completely abolished the ID constriction. A phentolamine injection, on the other hand, significantly attenuated the constriction with approximately half of the constriction persisting. The results indicate that an increase in vascular smooth muscle tone occurred in the small muscular pulmonary arteries, particularly those of 200-400 microns ID, in response to the acute rise of PAP above 30 mmHg during the LAP elevation. In addition, the data suggest the partial participation of catecholamines in the active contraction of vascular smooth muscle. The arterial contraction may serve to protect the pulmonary capillaries from an excessive hydrostatic pressure and pulmonary edema.     

Inhibitory effect of pentobarbital anesthesia on venous stasis induced arteriolar vasoconstriction in the dog hindleg

The effect of close intrarterial administration of pentobarbital in the concentration of about 2times10^-4 mol/1 on the venous stasis induced arteriolar constriction in the dog hindleg was studied in 6 neurolept anesthetized dogs. It was found that the blood flows and vascular resistances in the legs before pentobarbital infusion were equal and the vasoconstrictor responses to venous stasis were the same. Pentobarbital infusion into the femoral artery in one of the legs increased the total leg blood flow compared to the control leg and abolished the increase in vascular resistance during venous stasis. In another experimental series the effect of general pentobarbital anesthesia on the vasoconstrictor activity in response to venous stasis locally in subcutaneous and muscle tissue in the hind limb was examined in 6 dogs. It was found that during the first 2–3 h of anesthesia the vasoconstrictor response was present in both tissues although the response in muscle tissue exhibited a great variation between the dogs during this period. However, after 4–5 h of anesthesia the response was abolished in both tissues. During neurolept anesthesia with fentanyl/N₂O the same vasoconstrictor response was demonstrated in the hindleg 1 h and 5 h after induction of the anesthesia. It is concluded that pentobarbital anesthesia abolishes the arteriolar constriction induced by venous stasis. The mechanism may be blockade of the local sympathetic vasoconstrictor fibres or interference with myogenic vasoconstrictor mechanism of the vascular smooth muscle cells or both. It is suggested that fentanyl/N₂O anesthesia is better suited for this kind of studies.     

Responses of single arterioles in vivo in cat skeletal muscle to change in arterial pressure applied at different rates

The concept of a rate-dependent, dynamic as well as a static component in the myogenic control has been suggested in some previous in vitro and whole organ investigations. The present study is an attempt to reveal a dynamic component in the myogenic response directly on single arterioles by a vital microscopic technique. The study was made on the autonomically blocked vascular bed of cat tenuissimus muscle and performed by analysing the arteriolar diameter changes to an arterial pressure increase and decrease when applied at two different rates. The results demonstrate a transient, dynamic constrictor response upon the phasic increase in pressure and a transient, dynamic dilator response upon the phasic decrease in pressure, the magnitudes of which being related to the rate of the pressure change. The static response developing during the steady-state phase of constant increased pressure was also shown. The dynamic responses were confined to arterioles smaller than about 20 μm while the steady-state response was present in larger arterioles as well. Even if the metabolic control system partly could be responsible for the obtained responses, arguments are given that the described reactions are mainly myogenic in nature.     

Cerebral venous outflow and arterial microsphere flow with elevated venous pressure

The cerebral blood flow response to cerebral venous pressure elevation was studied in pentobarbital-anesthetized dogs using the cerebral venous outflow and radiolabeled microsphere techniques. Cerebral venous pressure elevation resulted in a significant reduction in cerebral venous outflow at a pressure of approximately 2.0 mmHg (referenced at the level of the external auditory meatus). At higher pressures, cerebral venous outflow decreased at a rate of 0.5 ml x min-1 x mmHg-1. Mean arterial pressure was 102.0 mmHg, and thus cerebral perfusion pressure (mean arterial pressure minus cerebral venous pressure) was well within the range for cerebral autoregulation. These results were obtained regardless of whether cerebrospinal fluid pressure was allowed to rise concomitantly with cerebral venous pressure (11 dogs) or was maintained at atmospheric pressure (7 dogs). However, simultaneous measurement of cerebral venous outflow and total and regional cerebral blood flow with the radiolabeled microsphere technique with venous pressure elevation (6 dogs) produced discrepant results. As cerebral venous pressure was elevated to approximately 16.0 mmHg, cerebral venous outflow decreased to 40% of control while total and regional cerebral blood flow values remained unchanged, so that regional and cerebral vascular resistances decreased. These results suggest that cerebral venous pressure elevation opens intracranial venous anastomotic channels and diverts blood flow from the measured venous drainage through other drainage sites. In addition, our results suggest that the dominant mechanism of cerebral autoregulation is metabolic, not myogenic.     

Changes in vasomotion pattern and local arteriolar resistance during stepwise pressure reduction

Changes in vasomotion parameters and their consequences for local arteriolar resistance were studied in transverse arterioles and their first order side branches in the tenuissimus muscle of 10 young urethane anesthetized rabbits during stepwise reduction of arterial pressure, using intravital microscopy. To assess the influence of vasomotion on mean local arteriolar resistance, the effective vascular diameter, as a measure of mean flow carrying capacity, was calculated. The contribution of vasomotion to the mean local resistance is limited in transverse arterioles, but important in first order side branches, dominating the flow fluctuations in the downstream capillaries.During pressure reduction, an over-all increase in vasomotion cycle length and amplitude was found in both transverse arterioles and first order side branches, concomitant with an increase in effective arteriolar diameter and a decrease in local blood flow and reduced velocity, as a measure of wall shear rate. Flow autoregulation was observed in 70% of the arterioles. The changes in cycle length and amplitude showed only limited correlations with local blood flow, reduced velocity, arterial pressure and effective arteriolar diameter. This indicates that it is unlikely that only one of these variables is responsible for the changes in the vasomotion parameters.Supported by Medigon/Zwo (Grant 900-517-157).     

Relation between capillary pressure and vascular tone over the range from maximum dilatation to maximum constriction in cat skeletal muscle

An attempt was made to assess, from a large sample (n = 567), the normal level of hydrostatic capillary pressure (Pc) in resting skeletal muscle and the extent of Pc regulation as effected by strictly graded activation of metabolic and adrenergic control mechanisms over the entire physiological range of vascular tone. With the use of a new whole-organ technique, Pc towards the venous end of the capillary was continuously recorded at constant arterial pressure (100 mmHg) and under simultaneous observations of total regional vascular resistance (RT), precapillary resistance (Ra) and post-capillary resistance (RV). In the control state with a Starling fluid equilibrium, a venous pressure of 7 mmHg and normal vascular tone (RT = 19.1 +/- 0.3 PRU), Pc averaged 16.7 +/- 0.3 mmHg. Graded metabolic dilatation (muscle exercise), decreasing RT to a minimum value of 1.7 PRU, caused progressive increase in Pc up to 32 mmHg and consequent fluid filtration. Conversely, graded adrenergic constriction, increasing RT to a maximum of 100 PRU, caused a progressive decrease in Pc down to 10 mmHg and consequent fluid absorption. The relation between Pc and RT was highly non-linear, Pc increasing more steeply the more RT approached low values, and was described by the power function: Pc = 36.43 x RT-0.27 (r = -0.79, P less than 0.001). The resistance ratio, Rv/Ra (the main determinant of Pc), and vascular tone (RT) showed a similar non-linear relation. Regulatory change of Rv/Ra was mainly accomplished by active change of Ra, but a pronounced Rv decrease (venodilatation) occurred in the lowest RT range, exerting a protective function against excessive increase in Pc and detrimental plasma fluid loss.     

Influence of Vessel Distension and Myogenic Tone on Pulmonary Arterial Input Impedance. A Study using a Computer Model of Rabbit Lung

A computer model of the pulmonary arterial (PA) bed of rabbit lungs was designed in order to test experimental observations of changes in PA input impedance and pulsatile hydraulic power (cap.) during increased PA pressure. The computer model was based on a simple 3-component analog representation of single vessels (i.e. resistance, inertance and compliance). 16 generations of arterial vessels, from PA to 60 μm diameter, were combined to calculate PA input impedance. Input impedance was found to mimic closely that observed experimentally. Both venous pressure elevation and arteriolar constriction was found to reduce input impedance and Wp. By combining arteriolar constriction with increased myogenic tone of the larger arteries, Wp was found to show a minimum level at a certain PA pressure, dependent on the degree of arterial stiffening. Wp was found to follow changes in arterial volume and resistance during simulated vasoconstriction. Wp dissipation in arterial vessels was calculated to approx. 50% of total input Wp at physiological pressure conditions, and could be reduced by one half after PA pressure increase from 20 to 50 cm H₂O, despite a concurrent halving of arterial compliance. Arterial vessels smaller than 200 pm diameter were found to have negligible direct influence on PA input impedance.     

Renal autoregulation: evidence for the transmural pressure hypothesis.

Autoregulation of glomerular filtration rate (GFR) was examined during uteral orarterial constriction in anesthetized dogs after renal denervation. GFR was sustaineduntil ureteral pressure greater than 80 mmHg, provided renal arterial pressure exceeded 180 mmHg, but fell at ureteral pressure less than 54 mmHg when arterial pressure averaged 127 plus or minus 5 mmHg; renal blood rose as GFR declined. Ethacrynic acid, saline, or mannitol infusion increased tubular pressure without reducing GFR,but during subsequent ureteral constriction GFR fell at uteral pressure less than 40mmHg. During arterial constriction GFR was maintained at lower arterial pressures in hydropenic than in diuretic dogs. Because of thisdifference in the range of autoregulation, saline infusion increased GFR more in hydropenic than in diuretic dogs except at high arterial pressure. This response to reduced plasma oncotic pressure and the constancy of GFR over a wide range of proximal tubular and arterial pressure indicate constancy of thehydrostatic transmural pressure of glomerular capillaries. Afferent arteriolar resistance is, in addition to a regulation by transmural pressure, perhaps controlled by vascular stretch receptors in the glomeruli.     

Renal and nephron hemodynamics in spontaneously hypertensive rats.

Renal and nephron hemodynamics were compared between anesthetized, nondiuretic, spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Although the mean arterial pressure was higher in SHR than in WKY, 158 VS. 114 mmHg, glomerular filtration rate (GFR) and renal blood flow (RBF) were similar in both groups. So were intrarenal hydrostatic pressures, single nephron GFR (SNGFR), and single nephron blood flow (SNBF). Accordingly, the increased renal vascular resistance (RVR) in SHR was due to predominant preglomerular vasoconstriction. In a second group of SHR, SHR-AC, the femoral arterial pressure was reduced acutely to 114 mmHg by means of aortic constriction above the renal arteries. The mean values for GFR, RBF, SNGFR, SNBF, and intrarenal hydrostatic pressures resembled those in SHR, whereas RVR was less in SHR-AC. These autoregulatory adjustments of RVR were again largely limited to the preglomerular vasculature. Efferent arteriolar resistance was similar in all three groups. We conclude that the enhanced RVR in 12-wk-old SHR is primarily a consequence of a physiological, autoregulatory response of afferent arteriolar resistance to the elevated arterial pressure. Further, RVR in SHR is not fixed and constant but responds appropriately to reductions in renal perfusion pressure.     

Local vascular responses to elevation of an organ above the heart

Elevation of an organ above the heart reduces the arterial and venous hydrostatic pressures in proportion to the height of elevation. Intact autoregulation protects organs, such as the brain and skeletal muscle, from significant alterations in blood flow and hydrostatic capillary pressure due to the decrease in arterial inflow pressure during such a manoeuvre. However, the consequences of the decreased hydrostatic pressure on the venous side are far from clarified. The present study analyses the local haemodynamic effects of the decrease in arterial and venous hydrostatic pressures that occur during vertical elevation of an organ above the heart at atmospheric and raised tissue pressures (0, 10 and 30 mmHg). A sympathectomized cat skeletal muscle enclosed in a plethysmograph and perfused from the animal was used as the experimental model. The results show that elevation of the muscle above the heart at atmospheric tissue pressure created a variable vascular resistance starting at the venous outlet of the organ, and related to the difference between tissue pressure and venous outflow pressure. This resistance completely protects the organ from the hydrostatic pressure alterations on the venous side. The results also show that arterial pressure variations will exert the same haemodynamic influences on the organ as tissue pressure variations, except for the formation of the venous outflow resistance at raised tissue pressure. The application of these results to normal and injured organs, e.g. normal and injured skeletal muscle and brain, with various tissue pressures, is discussed.     

Oxygen-dependent mechanisms in cerebral autoregulation

Autoregulatory adjustments in the caliber of cerebral arterioles were studied in anesthetized cats equipped with cranial windows for the direct observation of the pial microcirculation. Increased venous pressure caused slight, but consistent, arteriolar dilation, at normal and at reduced arterial blood pressure and irrespective of whether or not intracranial pressure was kept constant or allowed to increase. Arterial hypotension caused arteriolar dilation which was inhibited partially by perfusion of the space under the cranial window with artificial CSF equilibrated with high concentrations of oxygen. This vasodilation was inhibited to a greater extent by perfusion of the space under the cranial window with fluorocarbon FC-80, equilibrated with high concentrations of oxygen. CSF or fluorocarbon equilibrated with nitrogen did not influence the vasodilation in response to arterial hypotension. The response to increased venous pressure was converted to vasoconstriction when fluorocarbon equilibrated with high concentrations of oxygen was flowing under the cranial window. The vasodilation in response to arterial hypotension was inhibited by topical application of adenosine deaminase. The results show that both metabolic and myogenic mechanisms play a role in cerebral arteriolar autoregulation. Under normal conditions, the metabolic mechanisms predominate. The presence of the myogenic mechanisms may be unmasked by preventing the operation of the metabolic mechanisms. The major metabolic mechanism seems to be dependent on changes in PO₂ within the brain with secondary release of adenosine.     

Microvascular myogenic reaction in the wing of the intact unanesthetized bat.

Microvascular dimension and flow responses to stepwise changes in arterial and venous pressures, ranging from zero to +100 mmHg and zero to -75 mmHg have been recorded. Observations were made in arterioles, terminal arterioles, and precapillary sphincters in the wing web of intact, unanesthetized bats. The results show for all categories of vessels that with reduced transmural pressures there is a progressive increase in mean diameter and a decrease in rhythmic vasomotion rate. Flow changes are variable. For elevated transmural pressures there is a vasoconstriction with drastic flow reduction that is inconsistent with metabolic control. However, after prolonged elevation of pressure there is a progressive increase in flow, suggesting a "metabolic escape". Computed wall tension remains reasonably constant for a wide range of transmural pressures, suggesting that wall tension may be the controlled variable. These findings support the hypothesis of a myogenic reaction as a mechanism for maintenance of basal vascular tone in the intact unanesthetized bat.     

Effect of “Vein Pump” Activation upon Venous Pressure and Blood Flow in Human Subcutaneous Tissue

The effect of “vein pump” activation upon superficial venous pressure and blood flow in human subcutaneous adipose tissue was studied in 6 normals and 2 patients with venous insufficiency. Blood flow in subcutaneous tissue was measured at the lateral malleolus by the local ¹³³Xenon washout technique. with the subject placed in a supine position. During passive lowering of the leg blood flow decreased 50 per cent and total vascular resistance increased 136 per cent. Activation of the vein pump by continuously tipping the foot up and down caused a decrease in venous pressure of 5 mmHg in horizontal position. Venous pressure increased only by 8 mmHg when the leg was lowered during exercise. In this situation blood flow remained constant corresponding to an increase in vascular resistance of 42 per cent. However increasing venous pressure to 28 mmHg by venous stasis in the lowered leg during exercise caused an additional increase in vascular resistance of 82 per cent. In the patients with venous insufficiency exercise did not prevent the decrease in blood flow during lowering of the leg. Hence venous pressure elevation of 25 mmHg or more caused an additional increase in vascular resistance in subcutaneous tissue, “vasoconstrictor response”. It is concluded that this “vasoconstrictor response” depends on a vasoconstrictor impulse transmission from veins to arterioles, veno-arteriolar reflex.     

Cardiovascular responses to blockade of angiotensin and alpha-adrenergic receptors.

Both angiotensin and alpha-adrenergic blocking agents reduce arterial blood pressure in hypovolemic states. We have compared the effects of an angiotensin antagonist (saralasin) and an alpha-adrenergic blocking agent (phenoxybenzamine) in supramaximal dosage on cardiac output, total peripheral resistance, and venous tone in rabbits rendered hypovolemic by restriction of sodium intake, supplemented by a furosemide-induced diuresis 48 h prior to study. Saralasin (10 microgram/kg per min) reduced arterial blood pressure significantly (-15 +/- 1.2 mmHg) despite an unchanged cardiac output (P less than 0.025) due to a fall in total peripheral resistance. Phenoxybenzamine (5 mg/kg) induced a much larger fall in arterial blood pressure (-28 +/- 3.6 mmHg), despite an identical reduction in total peripheral resistance, because cardiac output also fell (+/- 9 ml/kg per min). The reduction in cardiac output was associated with a significant increase in hindlimb venous distensibility (P less than 0.001) after alpha-adrenergic blockade. Saralasin, conversely, had no influence on venous tone. Adrenergic mechanisms contribute to cardiovascular homeostasis through an influence on both arteriolar and venous tone, whereas the effect of angiotensin is directed entirely to the arteriolar side of the circulation.     

Myogenic vascular regulation in skeletal muscle in vivo is not dependent of endothelium-derived nitric oxide.

The hypothesis, based on in vitro experiments on large conduit arteries, that endothelium-derived nitric oxide is a mediator of vascular myogenic reactivity was tested in cat gastrocnemius muscle in vivo. This was done by comparing, in the absence and presence of effective endothelium-derived nitric oxide blockade by the specific inhibitors NG-monomethyl-L-arginine or NG-nitro-L-arginine methyl ester, myogenic responses in defined consecutive vascular sections to dynamic vascular transmural pressure stimuli, to arterial occlusion (reactive hyperaemia), and to arterial pressure changes (autoregulation of blood flow and capillary pressure). The results demonstrated that the myogenic vascular reactivity to quick ramp transmural pressure stimuli was not attenuated by endothelium-derived nitric oxide blockade, but rather reinforced. The amplitude of the reactive hyperaemia response was unaffected by endothelium-derived nitric oxide blockade, but its duration was shortened because of faster myogenic constriction, especially of large-bore arterial resistance vessels greater than 25 microns, in the recovery phase. Both the improved myogenic responsiveness to transmural pressure stimuli and the shortening of the reactive hyperaemia by endothelium-derived nitric oxide blockade suggested that endothelium-derived nitric oxide released in vivo acts as a 'metabolic' factor which certainly does not improve, but rather depresses myogenic vascular reactivity. Autoregulation of blood flow and capillary pressure were well preserved in the presence of endothelium-derived nitric oxide blockade. It was concluded from the results of these multifaceted tests that myogenic vascular regulation in skeletal muscle in vivo seems independent of endothelium-derived nitric oxide.(ABSTRACT TRUNCATED AT 250 WORDS)