Effects of heptanol on the neurogenic and myogenic contractions of the guinea-pig vas deferens. (17/10407)

1. The effects of the putative gap junction uncoupler, 1-heptanol, on the neurogenic and myogenic contractile responses of guinea-pig vas deferens were studied in vitro. 2. Superfusion of 2.0 mM heptanol for 20-30 min produced the following reversible changes in the biphasic neurogenic contractile response (8 trials): (i) suppression of both phases; (ii) delayed development of both the first as well as the second phase, accompanied by complete temporal separation of the two phases; (iii) prominent oscillations of force during the second (noradrenergic) phase only. 3. To eliminate prejunctional effects of heptanol, myogenic contractions were evoked by field stimulation of the vas in the presence of suramin (200 microM) and prazosin (1 microM). Heptanol (2.0 mM) abolished these contractions reversibly. 4. These results show that (i) heptanol inhibits both excitatory junction potential (EJP)-dependent and non EJP-dependent contractions of the vas; (ii) a postjunctional site of action of heptanol, probably intercellular uncoupling of smooth muscle cells, contributes to the inhibition of contraction.  (+info)

Protective effect of dietary tomato against endothelial dysfunction in hypercholesterolemic mice. (18/10407)

The effects of dietary ingestion of tomato were studied in mice that had been made hypercholesterolemic by feeding atherogenic diets. Mice which had been fed on the atherogenic diet without tomato for 4 months had significantly increased plasma lipid peroxide, and the vaso-relaxing activity in the aorta induced by acetylcholine (ACh) was harmed when compared with mice fed on a common commercial diet. On the other hand, mice which had been fed on the atherogenic diet containing 20% (w/w) lyophilized powder of tomato showed less increase in the plasma lipid peroxide level, and ACh-induced vaso-relaxation was maintained at the same level as that in normal mice. These results indicate that tomato has a preventive effect on atherosclerosis by protecting plasma lipids from oxidation.  (+info)

Effect of working hours on cardiovascular-autonomic nervous functions in engineers in an electronics manufacturing company. (19/10407)

A field survey of 147 engineers (23-49 years) in an electronics manufacturing company was conducted to investigate the effect of working hours on cardiovascular-autonomic nervous functions (urinary catecholamines, heart rate variability and blood pressure). The subjects were divided into 3 groups by age: 23-29 (n = 49), 30-39 (n = 74) and 40-49 (n = 24) year groups. Subjects in each age group were further divided into shorter (SWH) and longer (LWH) working hour subgroups according to the median of weekly working hours. In the 30-39 year group, urinary noradrenaline in the afternoon for LWH was significantly lower than that for SWH and a similar tendency was found in the LF/HF ratio of heart rate variability at rest. Because these two autonomic nervous indices are related to sympathetic nervous activity, the findings suggested that sympathetic nervous activity for LWH was lower than that for SWH in the 30-39 year group. Furthermore, there were significant relationships both between long working hours and short sleeping hours, and between short sleeping hours and high complaint rates of "drowsiness and dullness" in the morning in this age group. Summarizing these results, it appeared that long working hours might lower sympathetic nervous activity due to chronic sleep deprivation.  (+info)

Altered vascular reactivity following partial nephrectomy in the rat: a possible mechanism of the blood-pressure-lowering effect of heparin. (20/10407)

BACKGROUND: This study was designed to assess whether the antihypertensive effect of heparin in rats after renal mass reduction (RMR) is related to changes in nitric oxide activity, and to study in vitro the altered behaviour of resistance-sized arteries induced by chronic administration of heparin. METHODS: Male Wistar rats were assigned to one of two experimental protocols. In the first protocol, RMR rats received heparin (250 units/day s.c.) and tail systolic blood pressure (SBP) was measured weekly for 4 weeks. In a subgroup, urinary nitrate excretion (UNO3) and in vitro vascular reactivity of isolated perfused mesenteric arterial beds were measured 2 weeks after RMR. The second protocol assessed whether inhibition of NO synthesis with L-NAME (70 mg/l added to the drinking water) prevents the blood-pressure-lowering effect of heparin. RESULTS: In untreated RMR rats SBP increased from 111+/-3 mmHg to 127+/-5 mmHg at 2 weeks and 139+/-5 mmHg at 4 weeks. In contrast, in RMR rats treated with heparin, SBP was 114 +/-3 mmHg at 2 weeks and 115+/-4 mmHg at 4 weeks (P<0.05 for both). Treatment with L-NAME increased SBP both in untreated and heparin-treated RMR groups. Two weeks after nephrectomy daily urinary nitrate increased significantly more in RMR rats treated with heparin than in untreated RMR rats (22+/-2 vs 14.2+/-2.3 micromol/day, P<0.05). In vitro studies performed at 2 weeks showed that vessels of untreated RMR rats had a blunted vasodilator response to acetylcholine that was restored to levels similar to that of controls in the heparin-treated group. CONCLUSIONS: These results suggest that, in rats after renal ablation, heparin may exert its antihypertensive effect, at least in part, by affecting the altered behaviour of resistance vessels during the development phase of hypertension. Increased NO production may contribute to this effect.  (+info)

Maintenance of normal agonist-induced endothelium-dependent relaxation in uraemic and hypertensive resistance vessels. (21/10407)

BACKGROUND: The nitric oxide system has been implicated in several diseases with vascular complications including diabetes mellitus and hypertension. Despite the high prevalence of hypertension and cardiovascular complications in renal failure few studies have examined vascular and endothelial function in uraemia. We therefore chose to study possible abnormalities of the nitric oxide vasodilator system in an animal model of chronic renal failure. METHODS: Adult spontaneous hypertensive rats and Wistar Kyoto rats were subjected to a 5/6 nephrectomy with control animals having sham operations. After 4 weeks blood pressure was recorded and the animals were sacrificed. Branches of the mesenteric arteries were isolated and mounted on a Mulvany myograph. All experiments were performed in the presence of indomethacin (10(-5) M). The vessels were first preconstricted with noradrenaline, exposed to increasing concentrations of acetylcholine (10(-8) to 10(-4) M) and subsequently to sodium nitroprusside (10(-5) M). RESULTS: There was no difference in the relaxation of the four groups of vessels to any of the concentrations of acetylcholine used nor was there any significant difference in the EC50s (control Wistar Kyoto 6.1+/-1.4 x 10(-8) M; uraemic Wistar Kyoto 5.4+/-0.8 x 10(-8) M; control spontaneous hypertensive rats 4.5+/-0.6 x 10(-8) M; uraemic spontaneous hypertensive rats 6+/-0.7 x 10(-8) M). Vasodilatation in response to sodium nitroprusside was unchanged in uraemic vessels. In addition the vascular responses to both acetylcholine and sodium nitroprusside were unaltered in spontaneous hypertensive rats. CONCLUSIONS: We conclude that normal agonist-induced endothelium-dependent relaxation is maintained in experimental uraemia and hypertension.  (+info)

Lactate kinetics at rest and during exercise in lambs with aortopulmonary shunts. (22/10407)

In a previous study [G. C. M. Beaufort-Krol, J. Takens, M. C. Molenkamp, G. B. Smid, J. J. Meuzelaar, W. G. Zijlstra, and J. R. G. Kuipers. Am. J. Physiol. 275 (Heart Circ. Physiol. 44): H1503-H1512, 1998], a lower systemic O2 supply was found in lambs with aortopulmonary left-to-right shunts. To determine whether the lower systemic O2 supply results in increased anaerobic metabolism, we used [1-13C]lactate to investigate lactate kinetics in eight 7-wk-old lambs with shunts and eight control lambs, at rest and during moderate exercise [treadmill; 50% of peak O2 consumption (VO2)]. The mean left-to-right shunt fraction in the shunt lambs was 55 +/- 3% of pulmonary blood flow. Arterial lactate concentrations and the rate of appearance (Ra) and disappearance (Rd) of lactate were similar in shunt and control lambs, both at rest (lactate: 1, 201 +/- 76 vs. 1,214 +/- 151 micromol/l; Ra = Rd: 12.97 +/- 1.71 vs. 12.55 +/- 1.25 micromol. min-1. kg-1) and during a similar relative workload. We found a positive correlation between Ra and systemic blood flow, O2 supply, and VO2 in both groups of lambs. In conclusion, shunt lambs have similar lactate kinetics as do control lambs, both at rest and during moderate exercise at a similar fraction of their peak VO2, despite a lower systemic O2 supply.  (+info)

Spread of vasodilatation and vasoconstriction along feed arteries and arterioles of hamster skeletal muscle. (23/10407)

1. In arterioles of the hamster cheek pouch, vasodilatation and vasoconstriction can spread via the conduction of electrical signals through gap junctions between cells that comprise the vessel wall. However, conduction in resistance networks supplying other tissues has received relatively little attention. In anaesthetized hamsters, we have investigated the spread of dilatation and constriction along feed arteries and arterioles of the retractor muscle, which is contiguous with the cheek pouch. 2. When released from a micropipette, acetylcholine (ACh) triggered vasodilatation that spread rapidly along feed arteries external to the muscle and arterioles within the muscle. Responses were independent of changes in wall shear rate, perivascular nerve activity, or release of nitric oxide, indicating cell-to-cell conduction. 3. Vasodilatation conducted without decrement along unbranched feed arteries, yet decayed markedly in arteriolar networks. Thus, branching of the conduction pathway dissipated the vasodilatation. 4. Noradrenaline (NA) or a depolarizing KCl stimulus evoked constriction of arterioles and feed arteries of the retractor muscle that was constrained to the vicinity of the micropipette. This behaviour contrasts sharply with the conduction of vasodilatation in these microvessels and with the conduction of vasoconstriction elicited by NA and KCl in cheek pouch arterioles. 5. Focal electrical stimulation produced constriction that spread rapidly along feed arteries and arterioles. These responses were inhibited by tetrodotoxin or prazosin, confirming the release of NA along perivascular sympathetic nerves, which are absent from arterioles studied in the cheek pouch. Thus, sympathetic nerve activity co-ordinated the contraction of smooth muscle cells as effectively as the conduction of vasodilatation co-ordinated their relaxation. 6. In the light of previous findings in the cheek pouch, the properties of vasoconstriction and vasodilatation in feed arteries and arterioles of the retractor muscle indicate that substantive differences can exist in the nature of signal transmission along microvessels of tissues that differ in structure and function.  (+info)

Sympathetic nervous system activity and alpha-adrenergic responsiveness in older hypertensive humans. (24/10407)

We have previously demonstrated in normotensive humans an age-associated increase in sympathetic nervous system (SNS) activity combined with appropriate downregulation of alpha-adrenergic responsiveness. Impaired downregulation of alpha-adrenergic responsiveness, despite a comparable level of SNS activity, could contribute to higher blood pressure in older hypertensive humans. We measured arterial plasma norepinephrine (NE) levels and the extravascular NE release rate (NE2) derived from [3H]NE kinetics (to assess systemic SNS activity), and platelet and forearm arterial adrenergic responsiveness in 20 normotensive (N) and in 24 hypertensive (H), otherwise healthy, older subjects (60-75 yr). Although plasma NE levels were similar (N 357 +/- 27 vs. H 322 +/- 22 pg/ml; P = 0.37), NE2 tended to be greater in the hypertensive group (H 2.23 +/- 0.21 vs. N 1.64 +/- 0.20 microgram. min-1. m-2; P = 0. 11), and the NE metabolic clearance rate was greater (H 1,100 +/- 30 vs. N 900 +/- 50 ml/m2; P = 0.004). In the hypertensive group, there was a greater alpha-agonist-mediated inhibition of platelet membrane adenylyl cyclase activity and a NE- but not ANG II-mediated decrease in forearm blood flow. Compared with normotensive subjects, in older hypertensive subjects 1) NE metabolic clearance rate is increased, 2) systemic SNS activity tends to be increased, and 3) arterial and platelet alpha-adrenergic responsiveness is enhanced. These results suggest that heightened SNS activity coupled with enhanced alpha-adrenergic responsiveness may contribute to elevated blood pressure in older hypertensive humans.  (+info)