Pre- and postjunctional actions of hydralazine in vascular and nonvascular smooth muscle in vitro.
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This study investigated the in vitro prejunctional and postjunctional actions of hydralazine in vascular and nonvascular smooth muscle. Low concentrations (micromolar) of hydralazine blocked phenylephrine-induced increases in perfusion pressure in the innervated rat kidney, whereas high concentrations (greater than 10 microM) were required in the perfused, innervated rabbit ear artery. High concentrations of hydralazine were required to block phenylephrine-induced contractions of innervated rat vas deferens and anococcygeus muscle. After in vitro denervation, rabbit ear arteries became sensitive to low concentrations of hydralazine, but this was not observed in the rat vas deferens or anococcygeus muscle. Hydralazine (1-3 microM) was without effect on 3H-release from rat vas deferens, anococcygeus muscle and kidney previously incubated with [3H]norepinephrine. Hydralazine (1 microM) decreased field stimulation-induced 3H-release from [3H]norepinephrine-loaded rabbit ear arteries. The results from the rabbit ear artery confirm that in some vessels the presence of sympathetic nerve terminals can modify the postjunctional actions of low concentrations of hydralazine. However, the other vascular tissue studied (rat renal vascular bed) was sensitive to low concentrations of hydralazine while innervated. In conclusion, the existence of a postjunctional relaxant effect of hydralazine, observed in vitro at concentrations compatible with therapeutic blood levels found in humans, has been confirmed using two different vascular preparations. The relevance of the prejunctional effect of hydralazine remains to be ascertained.Keywords:
Hydralazine
Phenylephrine
Vas deferens
Vas deferens
Phenoxybenzamine
Hypogastric nerve
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Vas deferens
Vasectomy
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( Anesthesiology 2017;127:934–941) While phenylephrine is the established preferred vasopressor for maintaining blood pressure during spinal anesthesia for cesarean delivery, it is often associated with decreased heart rate and cardiac output. Both norepinephrine and phenylephrine are potent α-adrenergic agonists, yet norepinephrine also possesses weak β-adrenergic agonist activity. Recent studies have compared phenylephrine with norepinephrine; however, the doses of norepinephrine have varied. This random-allocation, graded dose-response study aimed to determine the relative potencies of norepinephrine and phenylephrine in treatment of hypotension during spinal anesthesia for cesarean delivery.
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Objectives: To Study the relationship between volume and anatomy of vas deferens. Design: Experimental studies on human vas deferens. Settings: Family planning clinics in Sichuan Province and laboratories in Sichuan Reproductive Health Institute. Subjects: 210 fresh vas samples from 107 volunteers of vasectomy. Method: The inner and outer equivalent diameters of vas deferens were measured by using computerized image graphic analysis technique with microphotography. The maximal volume of 1 cm vas deferens was determined by injection of colored solution. The histological observation of vas deferens rupture was conducted with continuous sections. Result: The average outer and inner diameters were 2.17±0.20 mm and 0.56±0.08 mm,respectively. The calculated thickness of vas wall was 0.81±0.21 mm.The average vas lumen volume vas lumen of was 0.05± 0.007ml.Different urpture manners of vas wall were found in histological observation. There is no significant relationship between the maximized vas volume and the anatomic parameters or physiologic characteristics,except the thickness of vas wall and the personal height. Conclusion:This study provides objective anatomic data about Chinese human vas deferens, and the maximal limit of vas volume in the 1 cm vas deferens. The diameter of vas deferens is not a suitable indicator for determination of injection volume in vas occlusion because only the thickness of the wall relates significantly to the vas volume.
Vas deferens
Vasectomy
Lumen (anatomy)
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Vas deferens
Blood supply
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C14-serotonin can be taken up by guinea-pig vas deferens tissue after an incubation in vitro. The accumulation is temperature-dependent and saturable and is blocked by cocaine, imipramine and ouabain, drugs known to interfere with the active transport of norepinephrine into the nerve cells, as well as by norepinephrine itself. The indoleamine appears to accumulate in the same intraneuronal sites which store endogenous norepinephrine. About half of the accumulated C14-serotonin is slowly released from the vas deferens within two hours. This release is enhanced by drugs which release norepinephrine, such as reserpine, tyramine, dopamine and norepinephrine. These observations suggest that uptake and storage in the sympathetic nerve terminals of peripheral tissues may not be specific processes for norepinephrine only, but for other normally occurring amines as well.
Vas deferens
Reserpine
Tyramine
Free nerve ending
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The effect of histamine on the field stimulated rat vas deferens preparation was studied and compared to mouse vas deferens. Histamine produced a concentration dependent inhibition of rat vas deferens (ID50 14 microM) similar to that seen with mouse vas deferens (ID50 2.4 microM). Unlike mouse however, where only H2 receptors are observed, the histamine inhibition of rat vas deferens was attenuated by both H1, (diphenhydramine) and H2 (cimetidine) antagonists. It is concluded that rat vas deferens contains both H1 and H2 receptor types.
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Cimetidine
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Levels of hydralazine in blood are log-linearly related to its vasodepressor effect. We examined the effect of oral dose size on the proportion of hydralazine that reaches systemic circulation. Nine subjects with hypertension were given hydralazine in oral doses in the therapeutic range. Blood hydralazine levels, effective liver blood flow, blood pressure, and heart rate were measured. As the hydralazine dose increased, the ratios of the AUC of hydralazine to hydralazine dose and of peak blood hydralazine concentration to hydralazine dose increased, indicating an increase in the proportion of the dose in blood. Liver blood flow tended to increase (maximum 40%) as dose increased above 0.5 mg/kg. Vasodepressor response and degree of tachycardia increased disproportionately with increasing hydralazine dose. There were strong log-linear relationships between peak hydralazine levels and both vasodepressor response and tachycardia that did not change with increasing hydralazine dose. Thus blood hydralazine and vasodepressor response increase disproportionately with increasing hydralazine doses in hypertension. Clinical Pharmacology and Therapeutics (1984) 36, 595–600; doi:10.1038/clpt.1984.227
Hydralazine
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After seven days of denervation there was a 10.7-fold increase in sensitivity without a significant alteration of the maximum response to norepinephrine (NE) in the guinea-pig vas deferens, in vivo. On the second postoperative day there was a significant increase in sensitivity and a decrease of the maximum response to NE in experiments performed in vivo. In the isolated guinea-pig vas deferens, immersed in Kreb's-Henseleit solution, an increased sensitivity to NE was demonstrable after two and seven days of denervation. However, an increased maximum response to NE was demonstrable only after seven days of denervation. Using McEwen solution there was no significant increase in the maximum response to NE in the seven-days denervated guinea-pig vas deferens. Slight alterations of the ionic composition of the physiological salt solutions prevented the demonstration of denervation-induced augmentation of the maximum response to NE in the isolated guinea-pig vas deferens. The characteristics of cocaine-induced supersensitivity to NE in the isolated guinea-pig vas deferens did not differ in vivo and were not affected by small changes in the ionic composition of the bathing solution. The absence of a postjunctional component of denervation supersensitivity to NE in the guinea-pig vas deferens, in vivo, is suggested. Furthermore, the demonstration of the postjunctional component of denervation supersensitivity to NE in the isolated guinea-pig vas deferens appears to be dependent of the composition of the bathing solution used.
Vas deferens
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