Positive effects of aggressive vasodilator treatment of well-treated essential hypertensive patients.

Increased systemic vascular resistance and coronary microvascular dysfunction are well-documented in essential hypertension (EH). We investigated the effect of additional vasodilating treatment on coronary and peripheral resistance circulation in EH patients with high systemic vascular resistance index (SVRI) despite well-treated blood pressure (BP). We enroled patients on stable antihypertensive treatment that were given intensified vasodilating therapy (ACE inhibitor, angiotensin II receptor blocker or calcium channel blocker). Before and following 6 months of intensified therapy, coronary resting and maximal artery flow were measured by transthoracic Doppler echocardiography to calculate coronary flow reserve (CFR) and minimum vascular resistance (C-Rmin). Cardiac output was estimated by inert gas rebreathing to calculate SVRI. Maximal forearm blood flow was determined by venous occlusion plethysmography to calculate minimum vascular resistance (F-Rmin). Patients were assigned into two groups: high-SVRI and low-SVRI subgroups, based on a median split at baseline. Following additional treatment SVRI decreased more in the high-SVRI group than in the low-SVRI group (14.4 vs -2.2%: P=0.003), despite similar baseline ambulatory BP (132/81 mm Hg) and BP reduction (6.5 and 4.6%: P=0.19). F-Rmin remained unchanged (6.5 vs -2.0%: P=0.30), while C-Rmin decreased by 22 and 24% (P=0.80) and CFR increased by 23 and 17% (P=0.16). Thus, intensified vasodilating therapy improved SVRI more in patients with high SVRI than in those with low SVRI. Regardless of SVRI status, the treatment improved cardiac but not forearm dilatation capacity. The substantial improvement of the hypertensive cardiac microvascular dysfunction was not related to the reduction in SVRI.

Antifibrotic effect after low-dose imatinib mesylate treatment in patients with nephrogenic systemic fibrosis: an open-label non-randomized, uncontrolled clinical trial.

BACKGROUND: Nephrogenic systemic fibrosis is a disease affecting the connective tissue of the skin and internal organs in patients with renal failure. No effective treatments are available. OBJECTIVES: To investigate if the tyrosine kinase inhibitor, imatinib mesylate was effective in patients with moderate to severe nephrogenic systemic fibrosis. METHODS: Among 25 patients with nephrogenic systemic fibrosis evaluated for the study from 1 October 2009 to 1 December 2010, four were included. They were treated with oral imatinib mesylate at a start dose of 400 mg/day. MAIN OUTCOME MEASURE: Reduction of skin fibrosis and increase in joint mobility evaluated by the modified Rodnan skin score and a goniometer. RESULTS: In two patients, the imatinib mesylate dose was reduced to 200 mg/day and in one patient to 100 mg/day. Two patients were treated for 24 weeks, one patient for 16 weeks and one patient for 4 weeks. Three patients experienced tethering of their skin which lessened with reduction in modified Rodnan skin score from 24 to 20, 24 to 17 and 21 to 14 but with very limited changes in joint mobility. The fourth patient discontinued the treatment due to a complicating infection. CONCLUSION: Imatinib mesylate may be an effective drug in the treatment of skin fibrosis in moderate to severe NSF cases, even at reduced doses. We found a positive clinical effect on the skin, but no convincing improvement of the joint mobility. Only few patients could be recruited limiting the interpretation and conclusions of the results.

Elevated pressure selectively blunts flow-evoked vasodilatation in rat mesenteric small arteries.

BACKGROUND AND PURPOSE: The present study investigated mechanisms underlying impaired endothelium-dependent vasodilatation elicited by elevating the intraluminal pressure in rat mesenteric small arteries. EXPERIMENTAL APPROACH: Arterial segments (internal diameter 316+/-2 microm, n=86) were mounted in a pressure myograph. The effect of elevating pressure from 50 to 120 mmHg for 1 h before resetting it to 50 mmHg was studied on endothelium-dependent vasodilatation. KEY RESULTS: In arteries constricted with U46619 in the presence of indomethacin, shear stress generated by flow, evoked vasodilatation that was abolished by an inhibitor of nitric oxide (NO) synthase, asymmetric dimethylarginine (1 mM), whereas acetylcholine-induced vasodilatation was unchanged. After elevation of intraluminal pressure for 1 h and then resetting it to 50 mmHg, vasodilatation induced by shear stress and the NO donor, S-nitrosopenicillamine was inhibited, while vasodilatation induced by a guanylyl cyclase activator, BAY 412272, and acetylcholine was unaltered. Superoxide levels sensitive to polyethylene glycol superoxide dismutase were increased in segments exposed to elevated pressure. A superoxide scavenger, tempol (300 microM), a general endothelin receptor antagonist, SB 217242 and the selective ET(A) receptor antagonist, BQ 123 preserved shear stress-evoked vasodilatation. CONCLUSIONS AND IMPLICATIONS: The present study shows that transient exposure to an elevated intraluminal pressure selectively inhibits flow-evoked NO-mediated vasodilatation, probably through activation of endothelin receptors and increased formation of superoxide. In contrast, elevation of pressure did not affect the acetylcholine-evoked endothelium-derived hyperpolarizing factor type vasodilatation in mesenteric small arteries.

Forearm plethysmography in the assessment of vascular tone and resistance vasculature design: new methodological insights.

AIM: High peripheral resistance and structural alteration in resistance arteries are central phenomena in essential hypertension and have been widely examined by forearm venous occlusion plethysmography; at rest for studying vascular tone, and during reactive hyperaemia for studying vascular structure. This work concerns the influence of venous pressure on hyperaemic vascular resistance (Rmin), the reproducibility of hyperaemic and resting vascular resistances (Rrest) and the relation between forearm and total peripheral vascular resistance (TPR). METHODS: In four healthy subjects, intravenous and intra-arterial blood pressures were measured simultaneously with plethysmographic recordings of hyperaemic and resting forearm blood flows. Reproducibility was examined in 15 young and 14 middle-aged healthy subjects and in 21 untreated hypertensive patients. RESULTS: Rmin remained low in the first recorded cardiac cycle, but rose in the second, even though corrected for the venous pressure rise, suggesting vascular tone recovery along with venous congestion. Between-day reproducibility of Rmin was high in middle-aged normotensive (8.7%) and hypertensive subjects (10.6%), but Rmin fell significantly between successive days in the young subjects. Rrest correlated with TPR, but required up to 40 min to reach steady state and showed high day-to-day variation in young (21.8%) and hypertensive subjects (16.2%). CONCLUSIONS: During hyperaemia, vascular resistance should be measured in the first cardiac cycle following venous occlusion to minimize influences of venous pressure rise and possible tone recovery. Rrest seems to reflect TPR. About 20 subjects may be needed to detect 15% changes between days in Rrest, fewer when concerning Rmin and TPR.

Statins decrease bone turnover in postmenopausal women: a cross-sectional study.

BACKGROUND: Statins have been suggested as potential agents in the management of osteoporosis. Reviews of medical records have shown an increased bone mass and some studies have shown a reduced occurrence of fractures in subjects on long-term treatment with statins. We studied the effects of treatment with statins on calcium homeostasis, bone turnover and bone mineral density. DESIGN: In a cross-sectional design, plasma levels of parathyroid hormone (PTH) and biochemical markers of bone turnover, bone mineral density (BMD) and body composition (fat- and lean tissue-mass) were measured in 140 postmenopausal women who had been treated with a statin for more than 2 years (median 4 years) and compared to 140 age- and gender-matched, population-based controls. RESULTS: Plasma levels of bone turnover markers were lower in the statin-treated subjects than in the controls: osteocalcin (-9%, P = 0.03), bone-specific alkaline phosphatase (-14%, P < 0.01), and C-terminal telopeptide of type I collagen (-11%, P < 0.01). On the other hand, plasma PTH levels were 16% higher in the statin-treated subjects than in the controls (P < 0.01). However, body composition and BMD at the lumbar spine, hip, forearm and whole body did not differ between the two groups. No correlation could be demonstrated between changes in biochemical quantities and dose or duration of statin use. CONCLUSION: Our data show that statins affect the function of bone cells. Most likely, the effect is antiresorptive.

Influence of nitric oxide synthase and adrenergic inhibition on adenosine-induced myocardial hyperemia.

BACKGROUND: Myocardial perfusion during adenosine-induced hyperemia is used both in clinical diagnosis of coronary heart disease and for scientific investigations of the myocardial microcirculation. The objective of this study was to clarify whether adenosine-induced hyperemia is dependent on endothelial NO production or is influenced by adrenergic mechanisms. METHODS AND RESULTS: In 12 healthy men, myocardial perfusion was measured with PET in 2 protocols performed in random order, each including 3 perfusion measurements. First, perfusion was measured at rest. Second, either saline or the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 4 mg/kg) was infused, and perfusion during adenosine-induced hyperemia was determined. Last, in both protocols, the alpha-receptor blocker phentolamine was infused, and perfusion during adenosine-induced hyperemia was determined again. Resting perfusion was similar in the 2 protocols (0.69+/-0.14 and 0.66+/-0.18 mL. min(-1). g(-1)). L-NAME increased mean arterial blood pressure by 12+/-7 mm Hg (P<0.01) and reduced heart rate by 16+/-7 bpm (P<0.01). Adenosine-induced hyperemia (1.90+/-0.33 mL. min(-1). g(-1)) was attenuated by L-NAME (1.50+/-0.55 mL. min(-1). g(-1), P<0.01). The addition of phentolamine had no effect on the adenosine-induced hyperemia (2.10+/-0.34 mL. min(-1). g(-1), P=NS). In the presence of L-NAME, however, when the adenosine response was attenuated, phentolamine was able to increase hyperemic perfusion (2.05+/-0.44 mL. min(-1). g(-1), P<0.05). CONCLUSIONS: Inhibition of endogenous NO synthesis attenuates myocardial perfusion during adenosine-induced hyperemia, indicating that coronary vasodilation by adenosine is partly endothelium dependent. alpha-Adrenergic blockade has no effect on adenosine-induced hyperemia unless NO synthesis is inhibited.

Peripheral flow response to transient arterial forearm occlusion does not reflect myocardial perfusion reserve.

BACKGROUND: Ultrasonographic evaluation of systemic arterial function is widely available, and a close relation of endothelial function in the coronary and brachial arteries has been documented. It is unknown, however, whether a similar correlation exists for their 2 microcirculatory territories and thus whether assessment of the systemic microcirculation can be used similarly as a surrogate marker of myocardial perfusion. METHODS AND RESULTS: Twenty-three patients with documented coronary artery disease (CAD; 66+/-9 years old, 18 men), 16 patients with syndrome X (SX; 56+/-5 years old, 13 women), and 45 healthy control subjects (C; 34+/-9 years old, 22 men) were studied. Myocardial perfusion was measured at rest and after dipyridamole (0.56 mg. kg(-1). min(-1) over 4 minutes) by PET, and brachial artery blood flow was measured at rest and after transient forearm ischemia by standard Doppler ultrasound techniques. Dipyridamole increased myocardial perfusion in all groups (mL. g(-1). min(-1): CAD, 0.89+/-0.27 versus 1.62+/-0.67, P:<0.001; SX, 0.82+/-0.16 versus 1.67+/-0.49, P:<0.001; and C, 0.82+/-0.15 versus 2.32+/-0.64, P:<0.001). Postocclusion forearm flow increased similarly in all groups (CAD, 52+/-18 versus 174+/-77 mL/min, P:<0.001; SX, 49+/-29 versus 202+/-82 mL/min, P:<0.001; and C, 61+/-34 versus 229+/-108 mL/min, P:<0.001). No significant correlations were found between peripheral and myocardial microcirculatory beds for either resting flow, hyperemic flow, or flow reserve in any of the groups (r(2)<0.1, P:=NS). CONCLUSIONS: The peripheral perfusion responses to transient forearm ischemia do not correlate with dipyridamole-induced myocardial hyperemia. The lack of correlation indicates different mechanisms of microvascular activation or regulation and confirms that extrapolations between findings in the 2 vascular beds are not suitable.

Nitric oxide, prostanoid and non-NO, non-prostanoid involvement in acetylcholine relaxation of isolated human small arteries.

The main purpose of the study was to clarify to which extent nitric oxide (NO) contributes to acetylcholine (ACh) induced relaxation of human subcutaneous small arteries. Arterial segments were mounted in myographs for recording of isometric tension, NO concentration and smooth muscle membrane potential. In noradrenaline-contracted arteries, ACh induced endothelium-dependent relaxations. The NO synthase inhibitor, N(G)-nitro-L-arginine (L-NOARG) had a small significant effect on the concentration-response curves for ACh, and in the presence of L-NOARG, indomethacin only caused a small additional rightward shift in the ACh relaxation. The NO scavenger, oxyhaemoglobin attenuated relaxations for ACh and for the NO donor S-nitroso-N-acetylpenicillamine (SNAP). Inhibition of guanylyl cyclase with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ), and inhibition of protein kinase G with beta-phenyl-1, N2-etheno-8-bromoguanosine- 3', 5'- cyclic monophosphorothioate, Rp-isomer, slightly attenuated ACh relaxation, but abolished SNAP induced relaxation. ACh induced relaxation without increases in the free NO concentration. In contrast, for equivalent relaxation, SNAP increased the NO concentration 32+/-8 nM. ACh hyperpolarized the arterial smooth muscle cells with 11.4+/-1.3 mV and 10.5+/-1.3 mV in the absence and presence of L-NOARG, respectively. SNAP only elicited a hyperpolarization of 1.6+/-0.9 mV. In the presence of indomethacin and L-NOARG, ACh relaxation was almost unaffected by lipoxygenase inhibition with nordihydroguaiaretic acid, or cytochrome P450 inhibition with 17-octadecynoic acid or econazole. ACh relaxation was strongly reduced by the combination of charybdotoxin and apamin, but small increments in the extracellular potassium concentration induced no relaxations. The study demonstrates that the NO/L-arginine pathway is present in human subcutaneous small arteries and to a limited extent is involved in ACh induced relaxation. The study also suggests a small contribution of arachidonic acid metabolites. However, ACh relaxation is mainly dependent on a non-NO, non-prostanoid endothelium dependent hyperpolarization. British Journal of Pharmacology (2000) 129, 184 - 192

Effect of short- and long-term heart failure on small artery morphology and endothelial function in the rat.

Chronic heart failure (HF) is associated with hemodynamic changes and activation of several neurohormonal systems, which are able both to inhibit and to facilitate arterial growth or remodeling and also to influence endothelial function. As these vascular changes may depend on the duration of HF, we evaluated morphologic and endothelial functional alterations in a rat model of HF after a short and long duration of HF. Rats with coronary ligation and sham-operated controls were investigated either 8 or 26 weeks after the operation with measurements of hemodynamics and isolated mesenteric small artery morphology and endothelial function. The effect of HF and duration of HF were examined by using two-way analysis of variance (ANOVA). HF rats had altered hemodynamics with reductions in cardiac output, left ventricular systolic pressure, and mean blood pressure, whereas left ventricular diastolic pressure was increased. HF caused remodeling of anatomically well-defined mesenteric small arteries with a reduction in media thickness and media-to-lumen ratio, but without change in the media cross-sectional area. Neither HF nor time had any influence on sensitivity or maximal relaxation to acetylcholine in the presence of indomethacin, but HF reduced vasoconstriction due to nitric oxide synthase blockade with N(G)-nitro-L-arginine independent of time. Our results indicate that HF, induced by coronary ligation in the rat, has a remodeling effect on mesenteric small arteries. However, the remodeling is moderate compared with that observed in hypertension. Furthermore, our results suggest that HF reduces basal release of NO.

In vitro simultaneous measurements of relaxation and nitric oxide concentration in rat superior mesenteric artery.

1. The relationship between nitric oxide (NO) concentration measured with an NO-specific microelectrode and endothelium-dependent relaxation was investigated in isolated rat superior mesenteric artery contracted with 1 microM noradrenaline. 2. Acetylcholine (10 microM) induced endothelium-dependent simultaneous increases in luminal NO concentration of 21 +/- 6 nM, and relaxations with pD2 values and maximum of 6.95 +/- 0.32 and 97.5 +/- 0.7 % (n = 7), respectively. An inhibitor of NO synthase, N G-nitro-L-arginine (L-NOARG, 100 microM) inhibited the relaxations and increases in NO concentration induced by acetylcholine. 3. Oxyhaemoglobin (10 microM) reversed the relaxations and increases in NO concentrations induced by acetylcholine, S-nitroso-N-acetylpenicillamine (SNAP) and S-morpholino-sydnonimine (SIN-1), but not the relaxations induced with forskolin. Oxyhaemoglobin also decreased the NO concentration below baseline level. 4. In the presence of L-NOARG (100 microM), a small relaxation to acetylcholine (10 microM) of noradrenaline-contracted segments was still seen; oxyhaemogobin inhibited this relaxation and decreased the NO concentration by 14 +/- 4 nM (n = 4). 5. The NO concentration-relaxation relationship for acetylcholine resembled that for SNAP and SIN-1 more than for authentic NO. Thus while 7-17 nM NO induced half-maximal relaxations in response to SNAP or SIN-1, 378 +/- 129 nM NO (n = 4) was needed for half-maximal relaxation to authentic NO. 6. The present study provides direct evidence that the relaxation of the rat superior mesenteric artery with the endothelium-dependent vasodilator acetylcholine is correlated to the endogeneous release of NO. The study also suggests that NO mediates the L-NOARG-resistant relaxations in this artery, and that there is a basal NO release.

Reduced vasodilator capacity in syndrome X related to structure and function of resistance arteries.

The combination of angina pectoris, angiographically normal epicardial coronary arteries, and a positive exercise test is referred to as syndrome X. Previous studies have demonstrated an impaired coronary flow reserve and a peripheral vascular dysfunction, suggesting that vascular abnormalities in syndrome X may not be confined to the heart. The aim of this study was to investigate whether any vascular disorder of syndrome X is due to intrinsic structural or functional disturbances in resistance arteries. We compared 16 patients with syndrome X (56.6+/-1.2 years, 3 men) with 15 matched control subjects. Myocardial blood flow was measured with 13N-ammonia positron emission tomography. Forearm blood flow was measured in the brachial artery with high-resolution ultrasound. Gluteal subcutaneous resistance arteries were dissected and mounted on a myograph for measurement of active tension development, lumen diameter, and media thickness. Baseline myocardial blood flow was similar in patients and controls, but dipyridamole-induced hyperemia was decreased in patients (1.67+/-0.13 vs 2.31+/-0.12 ml/ min/g, p <0.01). Patients and controls had similar baseline forearm blood flow, but hyperemic flow after transient occlusion of the brachial artery was impaired in patients (198+/-20 vs 273+/-32 ml/min, p <0.05). Isolated resistance arteries showed no differences in constriction to noradrenaline, or relaxation to acetylcholine, dipyridamole, or nitroglycerin. Furthermore, the ratio between media thickness and lumen diameter were similar in syndrome X patients and controls. Our data show that when compared with a well-matched control group, syndrome X patients have a decreased coronary and peripheral vasodilator capacity. However, this is not reflected by functional abnormalities or structural changes as evaluated in subcutaneous resistance arteries. We conclude that syndrome X is not a generalized intrinsic abnormality of the resistance circulation.

Pharmacological characterization of coronary small arteries from pigs with chronic ischaemic myocardial remodelling.

1. The effect of chronic ischaemic myocardial remodelling on small coronary artery reactivity in vitro was studied in a newly developed pig model. 2. Pigs were subjected to selective intracoronary embolizations with microspheres in the left anterior descending artery and circumflex artery causing scattered myocardial fibrosis. After an observation period of 130 days, heart dimensions and ejection fraction were determined with magnetic resonance imaging. Small arteries were isolated from the left ventricle and mounted as ring preparations in a myograph. Control arteries were taken from matched non-embolized pigs. 3. Compared with control pigs, end-systolic and diastolic volumes increased and left ventricular mass nearly doubled in embolized pigs. This indicates substantial myocardial hypertrophy, as the fraction area of fibrosis was only 12%. 4. Coronary small arteries preconstricted with 30 mmol/l KCI showed a normal contractile response to acetylcholine and 5-hydroxytryptamine. Sensitivity of the relaxation to bradykinin was nearly 3-fold increased and also slightly enhanced to isoprenaline in arteries from embolized pigs compared with controls, whereas relaxation to 5-hydroxytryptamine in the presence of ketanserin was similar. After inhibition of nitric oxide synthase with NG-nitro-L-arginine the sensitivity to acetylcholine increased to a similar extent in arteries from embolized pigs and controls. NG-Nitro-L-arginine abolished the relaxing effects of bradykinin and of 5-hydroxytryptamine in the presence of ketanserin. 5. We conclude that both the contractile function of the smooth muscle cells and the endothelial production or action of nitric oxide is preserved or slightly enhanced in coronary small arteries from pigs with chronic myocardial remodelling.

Increase by lysophosphatidylcholines of smooth muscle Ca2+ sensitivity in alpha-toxin-permeabilized small mesenteric artery from the rat.

1. Pharmacological characterization of different lysophosphatidylcholines was performed based on their effect on the Ca2+ sensitivity of contraction in alpha-toxin-permeabilized rat mesenteric arteries. Furthermore, the effect of noradrenaline on [3H]-myristate-labelled lysophosphatidylcholine levels was assessed, to investigate whether lysophosphatidylcholines could be second messengers. 2. Palmitoyl or myristoyl L-alpha-lysophosphatidylcholine increased the sensitivity to Ca2+, whereas lysophosphatidylcholines containing other fatty acids had less or no effect. 3. L-alpha-phosphatidylcholine, L-alpha-glycerophosphorylcholine, palmitic acid, myristic acid and choline, potential metabolites of lysophosphatidylcholines, did not affect contractions. 4. Noradrenaline (GTP was required) and GTP gamma S increased the sensitivity to Ca2+, and GDP-beta-S inhibited the effect of noradrenaline. Lysophosphatidylcholines, however, had no requirement for GTP and caused sensitization in the presence of GDP-beta-S. 5. Calphostin C, a relatively specific protein kinase C inhibitor, did not affect contraction induced by Ca2+, but abolished the sensitizing effect of lysophosphatidylcholine. 6. Noradrenaline caused no measurable changes in the levels of [3H]-myristate-labelled phosphatidylcholine and lysophosphatidylcholine at 30 s and 5 min stimulation. 7. These results suggest that lysophosphatidylcholines can increase Ca2+ sensitivity through a G-protein-independent, but a protein kinase C-dependent mechanism. However, the role for lysophosphatidylcholines as messengers causing Ca2+ sensitization during stimulation with noradrenaline remains uncertain because no increase in [3H]-myristate labelled lysophosphatidylcholine could be measured during noradrenaline stimulation.

Differences in sensitivity of rat mesenteric small arteries to agonists when studied as ring preparations or as cannulated preparations.

1. Pharmacological experiments on vascular tissue are normally performed on isometric ring or strip preparations. The aim of this study was to compare the isometric characteristics with the characteristics obtained if vessels were examined under the more physiologically appropriate isobaric condition. 2. Rat mesenteric small arteries were mounted either on two steel wires for isometric force measurement (wire-myograph) or cannulated for measurement of the internal diameter under isobaric conditions (pressure-myograph). 3. The passive pressure-diameter characteristics of the small arteries were similar on the wire- and pressure-myograph (using the Laplace relation to convert wall tension-internal circumference data from the wire-myograph to effective pressure-diameter characteristics). 4. In cumulative concentration-response experiments with noradrenaline and phenylephrine, the threshold concentration was 8-10 times lower, and the EC50-concentration was 4-5 times lower, in the pressure myograph compared to the wire-myograph. Thus vessels were not only more sensitive on the pressure myograph, but the slopes of the concentration-response curves were less steep. Similar experiments with vasopressin also showed this difference in the threshold-concentration and slope, but EC50 concentrations were similar. 5. Cumulative concentration-response experiments with K+ showed no difference either in EC50 or in slope on the wire- and pressure-myographs. 6. On the wire-myograph, some vessels were stretched longitudinally (to mimic the longitudinal stretch which had to be used in the pressure-myograph to avoid buckling). Such stretch did not affect the passive characteristics. 7. The differences between the EC50 determined on the wire- and pressure-myographs as regards noradrenaline and phenylephrine were eliminated when neuronal noradrenaline uptake was inhibited by denervation. However, the slope of the concentration-response curves on the wire-myograph was not affected by denervation.8. When vessels were exposed to cocaine (3 MicroM) the noradrenaline concentration-response curves were the same on the wire- and pressure-myographs as regards both EC50 and slope.9. On the wire-myograph, the calcium antagonist, methoxyverapamil, (D600) reduced the maximal contractile effect of noradrenaline by 50%, but on the pressure-myograph D600 did not affect the maximal response.10. The present results show that results obtained from vascular tissue under isometric conditions may differ substantially from the characteristics which would be obtained under isobaric conditions.