Influence of acid-etching after grit-blasted on osseointegration of titanium dental implants: in vitro and in vivo studies.

Rough implant surfaces have shown improved osseointegration rates. In a majority of dental implants, the microrough surfaces are obtained by grit blasting and/or acid-etching. The aim of this contribution was to evaluate the effects of acid-etching, after the grit-blasted treatment in titanium dental implants, on surface wettability, surface energy, osteoblast responses and its osseointegration behavior. Four surfaces were studied: as-machined, acid-etched, micro-rough by grit-blasting and the combination grit-blasted surface with acid-etched. The surfaces with increasing roughness show more osteoblastic adhered cells. This effect was most pronounced on samples blasted and blasted with acid-etching. The roughness obtained by grit-blasting is the main factor in comparison with the acid etching treatment in the biological response. These results were confirmed in vivo tests and histological analysis. The results demonstrated that the combination of the grit-blasted and acid-etched accelerated lightly bone regeneration at the different periods of implantation in comparison with the grit-blasted implants.

U-46619-induced potentiation of noradrenergic constriction in the human saphenous vein: antagonism by thromboxane receptor blockade.

OBJECTIVE: We investigated the potentiating effect of U-46619, a synthetic analogue of thromboxane A(2) (TXA(2)), on the adrenergic responses in human saphenous vein. METHODS: Saphenous vein rings were obtained from 35 patients undergoing coronary artery bypass surgery. The rings were suspended in organ bath chambers for isometric recording of tension. RESULTS: U-46619 (10(-10)-3 x 10(-7) mol/l) produced concentration-dependent and endothelium-independent contractile responses. U-46619 (10(-10) mol/l) potentiated the contractions elicited by electrical stimulation and potassium chloride, and produced leftward shifts of the concentration-response curve for noradrenaline. The TXA(2) receptor antagonist SQ-30741 (10(-8) mol/l) prevented the potentiation evoked by U-46619. The dihydropyridine calcium antagonist nifedipine (10(-6) mol/l) did not affect the potentiation of electrical stimulation and noradrenaline induced by U-46619, but abolished the potentiation of U-46619 on KCl-induced contractions. CONCLUSIONS: U-46619 facilitates sympathetic neurotransmission and potentiates constrictor effects of noradrenaline in human saphenous veins through stimulation of TXA(2) receptors. These effects are independent of calcium entry through dihydropyridine calcium channels.

Influence of endothelial nitric oxide on adrenergic contractile responses of human cerebral arteries.

The present study was designed to investigate the influence of the endothelium and that of the L-arginine pathway on the contractile responses of isolated human cerebral arteries to electrical field stimulation (EFS) and norepinephrine. Rings of human middle cerebral artery were obtained during autopsy of 19 patients who had died 3-8 h before. EFS (1-8 Hz) induced frequency-dependent contractions that were abolished by tetrodotoxin, prazosin, and guanethidine (all at 10(-6) M). The increases in tension were of greater magnitude in arteries denuded of endothelium. N(G)-monomethyl L-arginine (L-NMMA 10(-4) M) potentiated the contractile response to EFS in artery rings with endothelium but did not influence responses of endothelium-denuded arteries. L-arginine (10(-4) M) reversed the potentiating effects of L-NMMA on EFS-induced contractions. Norepinephrine induced concentration-dependent contractions, which were similar in arteries with and without endothelium or in arteries treated with L-NMMA. Indomethacin (3 x 10(-6) M) had no significant effect on the contractile response to EFS or on the inhibition by L-NMMA of acetylcholine-induced relaxation. These results suggest that the contractile response of human cerebral arteries to EFS is modulated by nitric oxide mainly derived from endothelial cells; although adrenergic nerves appear to be responsible for the contraction, the transmitter involved in the release of nitric oxide does not appear to be norepinephrine. The effects of L-NMMA in this preparation appear to be due to inhibition of nitric oxide formation rather than caused by cyclooxygenase activation.

4-Hydroxynonenal, a lipid peroxidation product, induces relaxation of human cerebral arteries.

The relaxant effect of 4-hydroxynonenal (4-HNE), a lipid peroxidation product, on human cerebral arteries was studied. Addition of 4-HNE to artery rings promoted no contraction, and after stimulation with prostaglandin F2 alpha (PFG2 alpha; 10(-7)-3 x 10(-6) M), 100% relaxation was obtained with 3 x 10(-5) M 4-HNE. Inhibition of nitric oxide formation with NG-nitro-L-arginine methyl ester hydrochloride (L-NAME; (10(-4) M), as well as prostaglandin synthesis with indomethacin (3 x 10(-6) M), partially prevented 4-HNE-induced relaxation, but each of these substances separately failed to inhibit complete relaxation. Addition of both inhibitors together reduced 4-HNE-induced relaxation to approximately 50%, but relaxation could not be abolished. When the endothelium was removed, 4-HNE did not promote relaxation after PGF2 alpha stimulation. The possible roles of different intracellular signaling systems in the vascular effect of 4-HNE are discussed.

4-hydroxynonenal-induced relaxation of human mesenteric arteries.

The effect of 4-hydroxynonenal (4-HNE), a circulating lipid peroxidation product, on the vascular tone of human mesenteric arteries is studied. 4-HNE promotes relaxation of human mesenteric arterial rings in a concentration-dependent manner. Removal of the endothelium or treatment with N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME; 10(-4) M) partially prevented 4-HNE-induced relaxation, thus suggesting the intervention of nitric oxide from endothelial origin in the vascular effects of 4-HNE.

Inhibition of neuroeffector transmission in human vas deferens by sildenafil.

Sildenafil (0.1 - 30 microM), a cyclic GMP phosphodiesterase 5 (PDE 5) inhibitor, induced inhibition of electrically evoked contractions of ring segments of human vas deferens from 34 vasectomies. Zaprinast (0.1 - 100 microM), another PDE 5 inhibitor, and the nitric oxide (NO) donor sodium nitroprusside (SNP) (0.1 - 100 microM) had no effect on neurogenic contractions. The inhibition induced by sildenafil was not modified by the inhibitor of guanylate cyclase 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ) (1 - 30 microM) but it was abolished by the K(+) channel blockers tetraethylammonium (TEA, 1 mM), iberiotoxin (0.1 microM) and charybdotoxin (0.1 microM). Sildenafil, zaprinast and SNP did not affect the contractions induced by noradrenaline. SNP (10 microM) caused elevation of cyclic GMP levels that was potentiated by sildenafil (10 microM) and zaprinast (100 microM). ODQ (10 microM) inhibited the increase in cyclic GMP. Sildenafil inhibits adrenergic neurotransmission in human vas deferens. The inhibition is not related to accumulation of cyclic GMP but is probably due to activation of prejunctional large-conductance Ca(2+)-activated K(+) channels.

Relaxation of human isolated mesenteric arteries by vasopressin and desmopressin.

1. The effects of vasopressin and deamino-8-D-arginine vasopressin (DDAVP, desmopressin) were studied in artery rings (0.8-1 mm in external diameter) obtained from portions of human omentum during the course of abdominal operations (27 patients). 2. In arterial rings under resting tension, vasopressin produced concentration-dependent, endothelium-independent contractions with an EC50 of 0.59 +/- 0.12 nM. The V1 antagonist d(CH2)5Tyr(Me)AVP (1 microM) and the mixed V1-V2 antagonist desGly-d(CH2)5D-Tyr(Et)ValAVP (0.01 microM) displaced the control curve to vasopressin to the right in a parallel manner without differences in the maximal responses. In the presence of indomethacin (1 microM) the contractile response to vasopressin was significantly increased (P < 0.01). 3. In precontracted arterial rings, previously treated with the V1 antagonist, d(CH2)5Tyr(Me)AVP (1 microM), vasopressin produced endothelium-dependent relaxation. This relaxation was reduced significantly (P < 0.05) by indomethacin (1 microM) and unaffected by the V1-V2 receptor antagonist desGly-d(CH2)5D-Tyr(Et)ValAVP (1 microM) or by NG-nitro-L-arginine methyl ester (L-NAME, 0.1 mM). 4. The selective V2 receptor agonist, DDAVP, caused endothelium-independent, concentration-dependent relaxations in precontracted arterial rings that were inhibited by the mixed V1-V2 receptor antagonist, but not by the V1 receptor antagonist or by pretreatment with indomethacin or L-NAME. 5. Results from this study suggest that vasopressin is primarily a constrictor of human mesenteric arteries by V1 receptor stimulation; vasopressin causes dilatation only during V1 receptor blockade. The relaxation appears to be mediated by the release of vasodilator prostaglandins from the endothelial cell layer and is independent of V2 receptor stimulation or release of nitric oxide. In contrast, the relaxation induced by DDAVP is largely dependent on stimulation of V2 receptors.

Increased responsiveness of human pulmonary arteries in patients with positive bronchodilator response.

1. The effects of noradrenaline, endothelin-1, acetylcholine and sodium nitroprusside were studied in isolated pulmonary arteries obtained from 14 patients undergoing lobectomy for lung carcinoma. Seven patients had shown increased response to a bronchodilator test prior to operation. In the remaining patients (control) the bronchodilator test was negative. 2. Artery rings from patients with a positive bronchodilator response showed greater contraction to noradrenaline (pD2 = 6.44 +/- 0.1; Emax = 93 +/- 9% of response to 100 mM KCl) and endothelin-1 (pD2 = 8.92 +/- 0.1; Emax = 130 +/- 16%) than the rings from control patients (pD2 = 6.04 +/- 0.08; Emax = 56 +/- 8% for noradrenaline; pD2 = 8.29 +/- 0.1; Emax = 78 +/- 10% for endothelin-1). There was no significant difference in the contractile responses to 100 mM KCl between arteries from either group of patients. 3. Arterial rings from patients with a positive bronchodilator test achieved 96 +/- 3% of maximal relaxation in response to acetylcholine, whereas rings from control patients achieved a maximal relaxation of 72 +/- 5%. Rings from both the controls and the patients with a positive bronchodilator test achieved complete relaxation in response to sodium nitroprusside but pD2 values were significantly higher in patients with a positive bronchodilator test. 4. Removal of endothelium or treatment with NG-nitro-L-arginine methyl ester of artery rings from both the control and the patients with a positive bronchodilator test reduced the relaxation to acetylcholine (P < 0.05) but did not modify relaxation to sodium nitroprusside. 5. It is concluded that responsiveness of pulmonary arterial smooth muscle to dilator and constrictor agents is increased in patients showing reversibility of airway constriction. Thus hyperresponsiveness of airway smooth muscle may be associated with a similar phenomenon in the surrounding vascular smooth muscle.

Potentiation by vasopressin of adrenergic vasoconstriction in the rat isolated mesenteric artery.

1. The aim of the present study was to investigate in rat mesenteric artery rings whether low concentrations of vasopressin could modify the contractile responses to noradrenaline and electrical stimulation of perivascular nerves. 2. Vasopressin (10[10]-10[-7] M) caused concentration-dependent contractions (pD2 = 8.36+/-0.09). The V1-receptor antagonist d(CH2)5Tyr(Me)AVP (10[-9]-10[-8] M) produced parallel rightward shifts of the control curve for vasopressin. Schild analysis yielded a pA2 value of 9.83 with a slope of 1.10+/-0.14. 3. Vasopressin (3 x 10[-10] and 10[-9] M) caused concentration-dependent potentiation of the contractions elicited by electrical stimulation (2-8 Hz; 0.2 ms duration for 30 s) and produced leftward shifts of the concentration-response curve for noradrenaline. The V1-receptor antagonist induced concentration-dependent inhibitions of potentiation induced by vasopressin. The selective V1-receptor agonist [Phe2, Orn8]-vasotocin (3 x 10[10] and 10[-9] M) induced potentiation of electrical stimulation-evoked responses which was also inhibited in the presence of the V1 antagonist (10[-8] M). In contrast, the V2-receptor agonist deamino-8-D-arginine vasopressin (desmopressin 10[-8]-10[-7] M) did not modify the electrical stimulation-induced responses and the V2-receptor antagonist [d(CH2)5, D-Ile2, Ile4, Arg8]-vasopressin (10[-8]-10[-7] M) did not affect the potentiation evoked by vasopressin. 4. In artery rings contracted by 10(-6) M noradrenaline in the presence of 10(-6) M guanethidine and 10(-6) M atropine, electrical stimulation (2, 4 and 8 Hz) produced frequency-dependent relaxations which were unaffected by 10(-9) M vasopressin but abolished by 10(-6) M tetrodotoxin. 5. Vasopressin also potentiated contractions elicited by KCl and contractions induced by addition of CaCl2 to KCl depolarized vessels. The augmenting effects were inhibited by the V1 antagonist. 6. In the presence of the calcium antagonist nifedipine (10[-6] M), vasopressin failed to enhance the contractile responses to electrical stimulation, noradrenaline and KCl. 7. The results demonstrate that low concentrations of vasopressin strongly potentiate the contractions to adrenergic stimulation and KCl depolarization. This effect appears to be mediated by V1 receptor stimulation which brings about an increase in calcium entry through dihydropyridine-sensitive calcium channels.

Role of endothelium and calcium channels in endothelin-induced contraction of human cerebral arteries.

Endothelin constricted human isolated cerebral arteries in a concentration-dependent manner. The maximal tension developed, as well as EC50 values were similar in arteries with and without endothelium. Removal of extracellular calcium or addition of the calcium antagonist nicardipine (10(-6)M), attenuated but did not abolish responses to endothelin. These experiments show that the endothelin-induced contraction in human cerebral arteries is not linked to the presence of intact endothelial cells. The data also show that the contractile effects of endothelin cannot be explained solely by an action on voltage-dependent calcium channels.

Neurogenic contraction and relaxation of human penile deep dorsal vein.

1. The aim of the present study was to characterize neurogenic and pharmacological responses of human penile deep dorsal vein and to determine whether the responses are mediated by nitric oxide from neural or endothelial origin. 2. Ring segments of human penile deep dorsal vein were obtained from 22 multiorgan donors during procurement of organs for transplantation. The rings were suspended in organ bath chambers for isometric recording of tension. We then studied the contractile and relaxant responses to electrical field stimulation and to vasoactive agents. 3. Electrical field stimulation (0.5-2 Hz) and noradrenaline (3 x 10(-10)-3 x 10(-5) M) caused frequency- and concentration-dependent contractions that were of greater magnitude in veins denuded of endothelium. The inhibitor of nitric oxide synthesis NG-nitro-L-arginine methyl ester hydrochloride (L-NAME, l0(-4) M) increased the adrenergic responses only in rings with endothelium. 4. In preparations contracted with noradrenaline in the presence of guanethidine (10(-6) M) and atropine (10(-6) M), electrical stimulation induced frequency-dependent relaxations. This neurogenic relaxation was prevented by L-NAME, methylene blue (3 x 10(-5) M) and tetrodotoxin (10(-6) M), but was unaffected by removal of endothelium. 5. Acetylcholine (10(-8)-3 x 10(-5) M) and substance P (3 x 10(-11) -3 x 10(-7) M) induced endothelium-dependent relaxations. In contrast, sodium nitroprusside (10(-9)-3 x 10(-5) M) and papaverine (10(-8) 3 x 10(-5) M) caused endothelium-independent relaxations. 6. The results provide functional evidence that the human penile deep dorsal vein is an active component of the penile vascular resistance through the release of nitric oxide from both neural and endothelial origin. Dysfunction in any of these sources of nitric oxide should be considered in some forms of impotence.

Contractile effects of arginine analogues on human internal thoracic and radial arteries.

OBJECTIVES: Plasma levels of endogenous guanidino-substituted analogues of L -arginine are increased in various pathologic conditions. In the present study we determined the effects of some of these compounds on basal and stimulated release of nitric oxide in human internal thoracic and radial arteries. METHODS: Rings of human internal thoracic and radial arteries were obtained from 16 multiorgan donors. The rings were suspended in organ baths for isometric recording of tension. RESULTS: N(G)-monomethyl L -arginine (10(-6) to 10(-3) mol/L) and N(G),N(G)-dimethyl L -arginine (10(-6) to 10(-3) mol/L) caused concentration- and endothelium-dependent contractions. Maximal force of contractions for N(G)-monomethyl L -arginine and N(G),N(G)-dimethyl L -arginine in the internal thoracic artery were 18.0% +/- 4.3% and 17.8% +/- 3.8%, respectively, of the contraction to 100 mmol/L KCl, and those found in the radial artery were 9.6% +/- 2.5% and 9.1% +/- 2.4%, respectively. Aminoguanidine (10(-5) to 3 x 10(-3) mol/L) and methylguanidine (10(-5) to 3 x 10(-3) mol/L) produced endothelium-independent contractions. L -Arginine (10(-3) mol/L) prevented the contractions by N(G)-monomethyl L -arginine and N(G),N(G)-dimethyl L -arginine but did not change contractions induced by aminoguanidine and methylguanidine. N(G)-monomethyl L -arginine and N(G),N(G)-dimethyl L -arginine inhibited, in a concentration-dependent manner, the endothelium-dependent relaxation to acetylcholine in the internal thoracic artery and had little attenuating effect in the radial artery; aminoguanidine and methylguanidine were without effect. CONCLUSIONS: The results suggest that the contractions induced by N(G)-monomethyl L -arginine and N(G),N(G)-dimethyl L -arginine are due to inhibition of both basal and stimulated nitric oxide production, whereas aminoguanidine and methylguanidine do not affect the synthesis of nitric oxide. An increase in the plasma concentration of N(G)-monomethyl L -arginine and N(G),N(G)-dimethyl L -arginine is likely to represent a risk factor for abnormal vasomotor tone in conduit arteries used as coronary grafts.

V2-receptor-mediated relaxation of human renal arteries in response to desmopressin.

The effects of deamino-8-D-arginine vasopressin (desmopressin), a V2 receptor antidiuretic agonist, were studied in isolated rings from branches of renal arteries obtained from 22 patients undergoing nephrectomy. The rings were suspended in organ bath chambers for isometric recording of tension. In precontracted rings with norepinephrine (10(-6) to 3 x 10(-6) mol/L), desmopressin (10(-11) to 3 x 10(-7) mol/L) caused endothelium-dependent relaxation (81%+/-4% reversal of the initial contraction in arteries with endothelium; 20%+/-4% in arteries without endothelium; P < .05). The relaxation to desmopressin in rings with endothelium was reduced significantly by indomethacin (10(-6) mol/L) and unaffected by the inhibitor of nitric oxide synthase NG-nitro-L-arginine methyl ester (10(-4) mol/L). Two V1 receptor antagonists (a peptidic and a nonpeptidic) had no effect on desmopressin-induced relaxation. However, V2 receptor antagonists (three peptidic and a nonpeptidic) reduced significantly (P < .05) the maximal response to desmopressin. The results of this study show that desmopressin exerts powerful endothelium-dependent relaxation of human renal arteries, probably through stimulation of V2-like receptors that may bring about the release of dilating prostaglandins.

Relaxation induced by cGMP phosphodiesterase inhibitors sildenafil and zaprinast in human vessels.

BACKGROUND: Sildenafil is currently used in the treatment of erectile dysfunction. However, assessment of direct effects of sildenafil on coronary arteries and on arteries used as coronary grafts is unknown. This study was designed to investigate the effects of sildenafil on contracted human coronary, internal mammary, and radial arteries obtained from multiorgan donors. The observations were extended to forearm veins. Zaprinast was included in this study for comparison. METHODS: Segments of left coronary, internal mammary, and radial arteries, and forearm veins were obtained from 16 multiorgan donors. Vascular rings were suspended in organ bath chambers and isometric tension was recorded. Then the effects of sildenafil, zaprinast, and sodium nitroprusside on precontracted vessels were studied. RESULTS: Sildenafil (10(-8) - 3 x 10(-5) mol/L) caused concentration-dependent relaxation in the internal mammary arteries, radial arteries, and forearm veins. In the coronary arteries, sildenafil had a modest relaxant effect. In addition, sildenafil amplified the relaxation induced by sodium nitroprusside in all four vessels. Relaxation was unaffected by the inhibitor of nitric oxide synthase NG-monomethyl-L-arginine (10(-4) mol/L). Compared with zaprinast, sildenafil was eight to ten times more potent in terms of EC50 values. CONCLUSIONS: The direct relaxant effects of sildenafil together with its synergistic interaction with nitric oxide donors should be considered in patients undergoing coronary bypass surgery, patients with low blood pressure, and patients receiving antihypertensive regimes.

Rete mirabile of goat: in vitro effects of adrenergic stimulation.

The carotid rete of the goat, a network of small arteries, is placed in the pathway of the main arteries which supply the brain. This structure lies within the cavernous sinus on each side of the pituitary. The presence of a carotid rete in many mammals has led to frequent speculations about its physiological function. The present study was designed to examine comparatively the responsiveness of goat retial and cerebral arteries to direct or indirect adrenergic stimulation. The contractile response of isolated retial arteries (150-500 micron in external diameter) to norepinephrine (10(-8) - 10(-4)M), field electrical stimulation (2-16 c/s), and tyramine (10(-6) - 10(-3) M) was negligible. In contrast, cerebral arteries of 300-500 micron in external diameter exhibited dose- or frequency-dependent contractions qualitatively similar to those previously described in larger cerebral arteries. The norepinephrine content in the walls of retial arteries was about 13% of that measured in cerebral arteries. These results suggest that the role of the carotid rete in the regulation of resistance to blood flow during adrenergic stimulation is negligible or nonexistent.

Endothelium-dependent component in the contractile responses of human omental arteries to adrenergic stimulation.

The present study was designed to investigate the influence of endothelium-derived nitric oxide on the contractile responses of isolated human omental arteries to electrical field stimulation and noradrenaline. We measured isometric tension in artery rings obtained from portions of human omentum during the course of abdominal operations (32 patients). Electrical field stimulation induced frequency-dependent contractions which were abolished by tetrodotoxin (10(-6) M) and prazosin (10(-6) M), thus indicating that this effect was due to noradrenaline released from adrenergic nerves acting on alpha 1-adrenoceptors. The increases in tension induced by electrical field stimulation were of greater magnitude in arteries denuded of endothelium. NG-Nitro-L-arginine (L-NAME, 10(-4) M) potentiated the contractile response to electrical field stimulation in artery rings with endothelium but did not influence the contractile responses of endothelium-denuded arteries. The potentiation induced by L-NAME was completely reversed by L-arginine (10(-4) M), but not by D-arginine (10(-4) M). Contractile responses to noradrenaline were similar in arteries with and without endothelium. L-NAME (10(-4) M) had no significant effect on the contractile responses to noradrenaline. Our results suggest that electrical field stimulation releases endothelium-derived nitric oxide which inhibits the contractile responses of human omental arteries. The constrictor responses to noradrenaline are not modulated by the endothelium.

The human deferential artery: endothelium-mediated contraction in response to adrenergic stimulation.

The human vas deferens receives its blood supply from the deferential artery, a long vessel which usually arises from the superior vesical artery. To date no information is available on the responsiveness of this artery to adrenergic stimulation. In the present work the effects of electrical field stimulation and noradrenaline were studied isometrically in rings of human deferential artery obtained from patients undergoing radical cystectomy (n = 7) or prostatectomy (n = 10). Electrical field stimulation (1-8 Hz, 20 V, 0.25 ms for 30 s) caused frequency-dependent contractions that were abolished by guanethidine, tetrodotoxin or prazosin. Noradrenaline (10(-7)-10(-4) M) induced concentration-dependent contractions with an EC50 of 1.3 x 10(-5) M. The increases in tension induced by electrical field stimulation and noradrenaline were of greater magnitude in arteries denuded of endothelium. The inhibitor of nitric oxide synthesis, NG-nitro-L-arginine methyl ester (10(-4) M), potentiated the responses to electrical field stimulation and noradrenaline in artery rings with endothelium. The results indicate that the human deferential artery has a marked ability to contract in response to adrenergic stimulation; they also suggest that the endothelium may have an inhibitory effect on adrenergic responses due, at least in part, to the release of endothelial nitric oxide. These effects could play an important role in regulating blood flow to the vas deferens.

Vasopressin receptors involved in adrenergic neurotransmission in the circular muscle of the human vas deferens.

We studied the effects of vasopressin on the adrenergic responses of in vitro preparations of circular muscle from the vas deferens obtained from 28 men undergoing elective vasectomy. Vasopressin (3 x 10(-9)-3 x 10(-8) M) enhanced the phasic contractions elicited by electrical field stimulation and noradrenaline. This potentiation was blocked by the vasopressin V1 receptor antagonist d(CH2)5Tyr(Me)vasopressin (10(-6) M) but not by the vasopressin V2 receptor antagonist [d(CH2)5, D-Ile2,Ile4,Arg8]vasopressin (10(-6) M). The Ca2+ antagonist nifedipine (10(-6) M) did not affect the potentiation of electrical field stimulation induced by vasopressin and noradrenaline but reduced KCl-induced contractions and abolished the induction of phasic activity by vasopressin in the presence of KCl. The results demonstrate that vasopressin, in addition to its direct contractile effects, strongly potentiates contractions of human vas deferens elicited by adrenergic stimulation. Both the direct and indirect effects of vasopressin appear to be mediated by vasopressin V1 receptor stimulation and are independent of Ca2+ entry through dihydropyridine Ca2+ channels.

Contractile responses of human deferential artery and vas deferens to vasopressin.

We studied the effects of vasopressin on isolated rings of human deferential artery and vas deferens (prostatic portion) obtained from patients undergoing radical cystectomy (n = 11) or prostatectomy (n = 10). Ring segments of artery or vas deferens were studied in organ bath experiments at optimal resting tension. In artery rings, vasopressin produced concentration-dependent, endothelium-independent contractions with an EC50 of 4.5 x 10(-10) M. The presence of NG-nitro-L-arginine methyl ester hydrochloride (10(-4) M), an inhibitor of nitric oxide synthase, did not change significantly (P > 0.05) the vasopressin-induced contraction. In ring preparations of the prostatic part of the vas deferens, vasopressin induced phasic contractions with an EC50 of 7.0 x 10(-9) M. The vasopressin V1 receptor antagonist, d(CH2)5Tyr(Me)AVP (10(-8) and 10(-6)), displaced to the right in parallel the control curve to vasopressin in artery and vas deferens rings. These results indicate that vasopressin exerts a powerful constrictor action on human deferential artery and vas deferens by direct stimulation of V1 receptors. It is concluded that the deferential artery may dampen the passage of blood to the vas deferens in circumstances characterized by increased plasma vasopressin levels.

Endothelin-1-induced potentiation of adrenergic responses in the rabbit pulmonary artery: role of thromboxane A(2).

To examine whether low concentrations of endothelin-1 potentiate the vasoconstrictor response to adrenergic stimulation, we recorded the isometric response of rings of rabbit pulmonary artery to electrical stimulation and noradrenaline. Endothelin-1 (10(-10) M) potentiated the contractions induced by electrical stimulation and noradrenaline. The endothelin ET(B) receptor antagonist (2,6-dimethylpiperidinecarbonyl-gamma-methyl-Leu-N(in)-[Methoxycarbonyl]-D-Trp-D-Nle) (BQ-788, 10(-6) M), but not the endothelin ET(A) receptor antagonist cyclo(D-Asp-Pro-D-Val-Leu-D-TRP) (BQ-123, 10(-6) M), inhibited the potentiating effects of endothelin-1. Pretreatment with the cyclooxygenase inhibitor indomethacin, the thromboxane synthase inhibitor furegrelate and the thromboxane receptor antagonist [1S-[1alpha,2alpha(Z),3alpha,4alpha]]-7-[3-[[[[(1-oxoheptyl)amino]acetyl]amino] methyl]-7-oxabicyclo-[2.2.1]hept-2-yl]-5-heptenoic acid (SQ-30741) (all at 10(-5) M) prevented the potentiation induced by endothelin-1 on adrenergic stimulation. The Ca(2+) channel antagonist nifedipine (10(-6) M) did not affect the potentiation induced by endothelin-1. The results indicate that endothelin-1 potentiates the responses to electrical stimulation and noradrenaline by activating endothelin ET(B) receptors. This potentiation depends on the production of cyclooxygenase-generated factors, probably thromboxane A(2).