Erythropoietin does not induce vasoconstriction directly in human subcutaneous resistance arterioles.
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Arteries↗
Biomedical subjects
S J Bund
Publications and source records attributed to S J Bund.
The contractile effects of porcine tetradecapeptide renin substrate in human resistance vessels: evidence of activation by vascular wall renin and serine proteases.
In order to test the hypothesis that the contraction induced in human resistance arterioles by porcine tetradecapeptide renin substrate (TDP) is mediated by enzymes specific to the renin-angiotensin cascade, human resistance vessels from skin and subcutaneous fat were mounted in a myograph and exposed to TDP in the presence and absence of the human renin inhibitor H261, the serine protease inhibitor aprotinin, a polyclonal anti-human renin antibody and captopril. TDP induced a dose-dependent contraction that could be abolished by saralasin. The sensitivity to TDP was significantly attenuated by H261, aprotinin and combinations of captopril with aprotinin and captopril plus aprotinin and H261, as indicated by a significant reduction in pD2 (-log10ED50 [mmol/l]) for TDP. However, captopril alone was ineffective. It was concluded that at physiological pH, porcine TDP induces contraction in human resistance vessels by the action of enzymes not specific to the renin-angiotensin cascade. Whilst a clear inhibitory effect of H261 was demonstrated, a significant comparable inhibition by captopril and a polyclonal renin antibody was not observed. This may reflect the difficulty with which these inhibitors gain access to their intracellularly located substrates.
Electric Stimulation↗
Effects of drug treatment on human resistance arteriole morphology in essential hypertension: direct evidence for structural remodelling of resistance vessels.
To examine whether effective drug treatment would reverse the morphological changes in resistance arterioles which characterise untreated essential hypertension, the vessels' media thickness and contractility were measured before and after long-term treatment. Nine patients underwent skin biopsy before and after a mean 13 months of antihypertensive treatment (range 4-24 months). Subcutaneous resistance arterioles were dissected and mounted in a myograph. Treatment did not affect the shift in sensitivity to noradrenaline in the presence of cocaine, sensitivity to exogenously administered calcium, and the rate of relaxation after withdrawal of vasoconstrictor stimuli. The media/lumen ratio fell significantly (p = 0.011) owing to a significant regression in media thickness (p = 0.0195), but this was not complete. Thus, effective antihypertensive treatment can reverse some of the structural change observed in the untreated state, although it apparently does not affect calcium sensitivity or relaxation rate; these features are thought to be consequences of the disease after it has become established.
Antihypertensive Agents↗
Blood vessels and human essential hypertension.
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Antihypertensive Agents↗
Vasopressin-mediated contractions in mesenteric arteries from spontaneously hypertensive rats: differences in response compared with Wistar-Kyoto animals.
1. The sensitivity of mesenteric resistance arterioles to [arginine]vasopressin (AVP) was investigated in spontaneously hypertensive rats (SHR) and control Wistar-Kyoto rats (WKY). No difference in pAVP (-log dose of AVP producing 50% of the maximum response) was observed [SHR 0.21 +/- 0.03 m-units/ml (n = 10) vs WKY 0.15 +/- 0.06 m-units/ml (n = 9)], although SHR vessels exhibited greater absolute tension development. 2. Both strains of rat displayed tachyphylaxis to repeated stimulation with AVP, and oscillatory tension changes were observed in all vessels from SHR and rarely in WKY vessels at activating concentrations of AVP. 3. AVP did not elicit a contractile response after noradrenaline-induced calcium depletion. 4. After vessels were depleted of calcium by using a combination of calcium-free media and noradrenaline stimulation, restoration of calcium in the presence of AVP elicited a greater contractile response in SHR vessels. 5. The results therefore provide evidence for an increased calcium response to AVP in SHR resistance vessels, although this was only demonstrable by calcium recovery experiments.
Animals↗
Neurotransmission in human resistance arteries: contribution of alpha 1- and alpha 2-adrenoceptors but not P 2-purinoceptors.
The contribution of postjunctional alpha 1- and alpha 2-adrenoceptors and P2-purinoceptors to the neuroeffector response was examined in isolated segments of human subcutaneous resistance arteries. Electrical field stimulation (EFS, 20 V, 0.2 ms, 1-25 Hz) elicited a maximum contractile response which was 38.2 +/- 1.6% of that elicited by exogenously applied (5 microM) noradrenaline (n = 56). Tetrodotoxin (1 microM), used to inhibit neurotransmission, reduced the electrically evoked response to 24.7 +/- 4.4% (n = 10) of the control response. The alpha 1-adrenoceptor antagonist prazosin (1 microM) reduced the maximum EFS contractile response to 64.8 +/- 5.5% of the control response (n = 17). Application of the alpha 2-adrenoceptor antagonist yohimbine (0.1 microM) reduced the maximum EFS response to 68.2 +/- 8.2% of the control response (n = 9). In the presence of prazosin plus yohimbine at the above-mentioned concentrations the maximum response to EFS was reduced to 47.6 +/- 6.7% (n = 11). Responses following alpha-blockade were not statistically different from those in the presence of tetrodotoxin, but the mean responses indicate that a non-adrenergic component to the EFS response cannot be discounted. Desensitisation of P 2-purinoceptors with alpha, beta-methylene ATP had no effect on responses to EFS; therefore under the conditions studied these receptors do not appear to be involved in neurotransmission. These results confirm the presence of postjunctional alpha 1- and alpha 2-adrenoceptors in human resistance arteries and for the first time demonstrate that the postjunctional alpha 2-adrenoceptor is important in modulating vascular responses elicited by intramural sympathetic nerve fibres.
Adrenergic alpha-Antagonists↗
Mechanical properties of porcine small coronary arteries in one-kidney, one-clip hypertension.
The purpose of this study was to analyse the mechanical properties of small coronary arteries from pigs with one-kidney, one-clip hypertension and normotensive control animals and to determine whether these could contribute to vascular structural changes observed in hypertension. Small coronary artery wall tension-internal circumference relationships were determined for coronary arteries mounted in a myograph and used to calculate incremental elastic modulus-stress relationships for arteries from normotensive and hypertensive pigs. Wall tension-internal circumference relationships were shifted to the left in arteries from hypertensive pigs, but the stress-strain and incremental elastic modulus-stress relationships were not influenced by the increased blood pressure load. These data indicate that small coronary arteries from hypertensive pigs are not less distensible than those from normotensive controls. Therefore the previously reported increased media thickness:lumen diameter ratios in coronary arteries in this model of hypertension are not a consequence of abnormal elastic properties and can be ascribed to a remodelling process.
Animals↗
Myogenic tone in coronary arteries from spontaneously hypertensive rats.
The aims of this study were to investigate myogenic tone in cannulated coronary arteries from SHR (spontaneously hypertensive rats) and WKY (Wistar-Kyoto rats) at 5 and 20 weeks of age under pressurised no-flow conditions. Pressure-diameter relationships (20-200 mm Hg) were determined in the presence (active) and absence (passive) of calcium and myogenic tone at each pressure was calculated. Active, but not passive diameter-pressure relationships were significantly different between strains at both ages. Active diameters were similar between strains at pressures up to 140 mm Hg at 5 and 20 weeks. At higher pressures SHR arteries generated more tone. Maximum myogenic tone was similar between strains in spite of increased wall thickness in the SHR at both ages. Endothelium denudation increased myogenic tone to a greater extent in the SHR at both ages. Active diameters of endothelium-denuded SHR arteries were smaller than those of WKY in the range 20-120 mm Hg at 5 week and 20-80 and 160-180 mm Hg at 20 weeks. These results demonstrate that during both the developmental and established phases of hypertension, myogenic tone is not enhanced in intact SHR coronary arteries, except at the highest pressures. Following endothelium removal SHR arteries generated greater myogenic tone also at lower pressures. These data demonstrate a greater endothelium-mediated antagonism of myogenic tone in SHR coronary arteries.
Age Factors↗