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PubMed1994

Vasodilator action of the isopropyl ester of palmitoyl carnitine in the rat coronary circulation and mesenteric vascular bed.

The vasodilator action of the isopropyl ester of palmitoyl carnitine (P1Pi) has been examined in perfused rat hearts and mesenteric vessels. The coronary vasodilator effect P1Pi was not significantly inhibited by flurbiprofen (10 microM), BW755C (10 microM), glibenclamide (10 microM) or the bradykinin B2 receptor antagonist D-Arg0[Hyp3,Thi5,8,D-Phe7]bradykinin (1 microM), indicating that the action of P1Pi is not mediated via arachidonic acid metabolites, ATP-dependent K+ channels or bradykinin B2 receptors. L-NG-Nitro arginine (100 microM) did not inhibit the vasodilator action of P1Pi whilst superoxide dismutase (20 and 50 U.ml-1) attenuated its vasodilator action. Methylene blue (10 microM) caused inhibition in three out of four hearts, while haemoglobin (1 microM) caused an irreversible inhibition of the action of P1Pi which was associated with a depression of myocardial contractility. In air-damaged mesenteric vascular beds the vasodilator action of P1Pi was not attenuated, whilst that of acetylcholine was abolished. In K(+)-depolarised mesenteric vascular beds the constrictor action of Ca2+ was attenuated by P1Pi. Therefore the vasodilator effect of P1Pi appears to be the result of a direct effect on smooth muscle.

Adenosine Triphosphate↗

PubMed2004

[Evaluation of intestinal hyperaemia in inflamed bowel by high resolution Contrast Harmonic Imaging (CHI)].

AIM: Intestinal hyperaemia is a sign of active disease in the inflamed intestine which can be detected by Doppler sonography. This technique, however, can be jeopardized by tissue motion artefacts (peristalsis), and intramural enteric vessel perfusion may be below the detection threshold. Visualisation of vessels by Contrast Harmonic Imaging (CHI) at a low Mechanical Index (low MI) is not restricted by the limitations mentioned above. Contrast Harmonic Imaging at low MI of the intestinal wall has not yet been described with high frequency probes. We therefore evaluated the validity of this method for detecting hyperaemia of the intestinal wall. METHODS: CHI at low MI was performed with a 7.5 MHz ultrasound probe in 12 patients with signs of an inflamed intestine. The contrast agent BR 1 (4.8 ml) was injected intravenously. Contrast enhancement was quantified by analysing gray scale values before and after injection of BR 1 in regions of interest within the submucosal layer. RESULTS: At about 15 sec. after injection of BR 1, arterial inflow of the contrast agent with visualisation of the feeding mesenteric vessels and intense contrast of the submucosal lamina could be observed. An increase of the gray scale values within the ROI after contrast enhancement was detected in all patients. CONCLUSION: We have shown that CHI at low MI is technically feasible for the demonstration of increased intestinal perfusion in inflammatory bowel disease by using a high resolution ultrasound probe. One possible method of quantifying the contrast enhancement is the gray scale analysis of pixels in defined regions of interest within the submucosal layer.

Adult↗

PubMed1999

Dexamethasone inhibition of leucocyte adhesion to rat mesenteric postcapillary venules: role of intercellular adhesion molecule 1 and KC.

BACKGROUND: A previous study showed that the glucocorticoid dexamethasone, at doses of 100 microg/kg and above, inhibited leucocyte adhesion to rat mesenteric postcapillary venules activated with interleukin 1beta (IL-1beta), as assessed by videomicroscopy. AIMS: To identify whether the adhesion molecule, intercellular adhesion molecule 1 (ICAM-1), or the chemokine KC could be targeted by the steroid to mediate its antiadhesive effect. METHODS: Rat mesenteries were treated with IL-1beta (20 ng intraperitoneally) and the extent of leucocyte adhesion measured at two and four hours using intravital microscopy. Rats were treated with dexamethasone, and passively immunised against ICAM-1 or KC. Endogenous expression of these two mediators was validated by immunohistochemistry, ELISA, and the injection of specific radiolabelled antibodies. RESULTS: Dexamethasone greatly reduced IL-1beta induced leucocyte adhesion, endothelial expression of ICAM-1 in the postcapillary venule, and release of the mast cell derived chemokine KC. Injection of specific antibodies to the latter mediators was also extremely effective in downregulating (>80%) IL-1beta induced leucocyte adhesion. CONCLUSIONS: Induction by IL-1beta of endogenous ICAM-1 and KC contributes to leucocyte adhesion to inflamed mesenteric vessels. Without excluding other possible mediators, these data clearly show that dexamethasone interferes with ICAM-1 expression and KC release from mast cells, resulting in suppression of leucocyte accumulation in the bowel wall, which is a prominent feature of several gastrointestinal pathologies.

Animals↗

PubMed2003

Effect of hyperhomocystinemia and hypertension on endothelial function in methylenetetrahydrofolate reductase-deficient mice.

OBJECTIVE: We evaluated the effect of hyperhomocystinemia and angiotensin (Ang) II on vascular function and structure in methylenetetrahydrofolate reductase knockout mice (Mthfr+/-). METHODS AND RESULTS: Mthfr+/- and controls (Mthfr+/+) received Ang II (400 ng/kg per min SC) or saline (14 days). Blood pressure, similar in Mthfr+/- and Mthfr+/+, was increased by Ang II. Acetylcholine- and bradykinin-induced relaxations were impaired in mesenteric resistance arteries (pressurized myograph) in Mthfr+/- and in Ang II-infused Mthfr+/+ mice and additionally blunted in Ang II-infused Mthfr+/- mice. The inhibition by L-NAME on acetylcholine was reduced in Mthfr+/- and in Ang II-Mthfr+/+ and absent in Ang II-Mthfr+/- mice. In these groups, vitamin C improved the response to acetylcholine and restored the inhibition by L-NAME. The media to lumen ratio of small arteries, similar in Mthfr+/- and Mthfr+/+, was increased by Ang II. Vascular NADPH oxidase activity, similar in Mthfr+/- and Mthfr+/+, increased after Ang II infusion. Vascular xanthine oxidase activity was also similar in Mthfr+/- and Mthfr+/+. Superoxide production in the aorta was reduced by sepiapterin and by L-NAME, suggesting that reduced bioavailability of tetrahydrobiopterin and uncoupling of nitric oxide synthase were the origin of increased reactive oxygen species in this model. CONCLUSIONS: Mthfr+/- mice show endothelial dysfunction of mesenteric vessels probably attributable to a reduced nitric oxide bioavailability caused by oxidative excess due to uncoupling of nitric oxide synthase without vascular structural alterations. Concurrent Ang II-induced hypertension additionally reduced nitric oxide, increased NADPH oxidase activity, and induced structural alterations. Our findings suggest additive adverse effect of Ang II-dependent hypertension and hyperhomocystinemia on endothelial function.

Acetylcholine↗

PubMed1999

Elective surgical treatment of symptomatic chronic mesenteric occlusive disease: early results and late outcomes.

PURPOSE: The purpose of this study was to determine the safety and efficacy of the elective surgical treatment of symptomatic chronic mesenteric occlusive disease (SCMOD) and to identify the factors that influence the results of this procedure. METHODS: From 1977 to 1997, 85 patients (mean age, 62 years) underwent elective surgical treatment of SCMOD. The presenting symptoms were abdominal pain in 78 patients (92%) and weight loss in 74 patients (87%). The surgical procedures included retrograde bypass grafting in 34 patients (40%), antegrade bypass grafting in 24 patients (28%), transaortic endarterectomy in 19 patients (22%), local arterial endarterectomy with patch angioplasty in six patients (7%), thrombectomy alone in one patient (1%), and superior mesenteric artery reimplantation in one patient (1%). Thirty-five patients (41%) underwent concomitant aortic replacement. All the involved mesenteric vessels were revascularized in 21 patients (25%), whereas revascularization was incomplete for the remaining 64 patients (75%). Late information was available for all 85 patients at a mean interval of 4.8 years. RESULTS: There were seven early (<35 days) postoperative deaths (8%). The cumulative 5-year survival rate was 64% (95% confidence interval [CI], 53% to 75%), and the 3-year symptom-free survival rate was 81% (95% CI, 72% to 90%). Serious complications occurred in 28 patients (33%). The results of univariate analysis identified advancing age at operation (P <.001), cardiac disease (P =.03), hypertension (P =.03), and additional occlusive disease (P =.05) as variables associated with mortality. Concomitant aortic replacement (P =.037), renal disease (P =.011), advancing age ( P =.035), and complete revascularization ( P =.032) were associated with postoperative morbidity including mortality. Late recurrent mesenteric occlusive disease was seen in 21 patients (16 symptomatic and five asymptomatic). Nine patients (43%) died, and 8 patients (38%) required subsequent surgical or endovascular procedures to treat their recurrent lesions. The 3-year survival rate from recurrent mesenteric occlusive disease was 76% (95% CI, 66% to 86%). CONCLUSION: We conclude that the elective surgical treatment of SCMOD may be performed with reasonable early and late mortality rates and that most of the patients remain free from recurrent symptoms of mesenteric ischemia. Advancing age, cardiac disease, hypertension, and additional occlusive disease significantly influenced the overall mortality rates, and concomitant aortic replacement, renal disease, and complete revascularization were significantly associated with postoperative morbidity rates. Surveillance and appropriate correction of recurrent disease appear to be necessary for optimal long-term results.

Adult↗

PubMedDate not supplied

Dimethyl sulfoxide (DMSO) and glycerol, hydroxyl radical scavengers, impair platelet aggregation within and eliminate the accompanying vasodilation of, injured mouse pial arterioles.

The hydroxyl radical scavengers dimethyl sulfoxide (DMSO) and glycerol were effective inhibitors of platelet aggregation in an in vivo mouse model of pial arteriolar injury. Aggregability was expressed in terms of the time required for a noxious stimulus (light + dye) to initiate aggregation. These drugs, given 1 hour before the injury, also eliminated the dilation which accompanied the damage. The same drugs failed to influence the constriction which accompanied an identical injury to mouse mesenteric arterioles, but again impaired platelet aggregation in the damaged mesenteric vessel. The data support the concept recently introduced by others, that, in the brain, hydroxyl radicals may mediate vascular damage and/or dilation accompanying the damage. The data also support the concept platelet aggregation may be stimulated, directly or indirectly, by hydroxyl radical. The effects of DMSO and glycerol in this study, irrespective of the molecular basis for the effects, may be relevant to the reported therapeutic benefit of these agents in cerebrovascular disease.

Animals↗

PubMed1977

Selective stimulation of venous prostaglandin E 9-ketoreductase by bradykinin.

The effects of bradykin on prostaglandin metabolism in canine mesenteric vessels were examined. Bradykinin stimulated microsomal prostaglandin synthesis in both artery and vein; this stimulation was more pronounced when [14C] hosphatidylcholine rather than [14C] arachidonate was used as the substrate for prostaglandin synthetase. This suggested that bradykinin enhanced a membrane phospholipase. In addition, bradykinin selectively stimulated prostaglandin E 9-ketoreductase activity from veins but not arteries. This may explain the finding that bradykinin induces the release of prostaglandin E compounds from arteries but prostaglandin F compounds from veins.

Alcohol Oxidoreductases↗

PubMed1989

Effect of a chronic infusion of atrial natriuretic factor on glomerular and vascular receptors in spontaneously hypertensive rats.

To investigate the effect of a prolonged infusion of atrial natriuretic factor (ANF) on its vascular and glomerular receptors, ANF (Ser 99-Tyr 126) was chronically administered (100 ng/h) for 7 days by osmotic minipumps to spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Blood pressure in the SHR fell from 149 +/- 5 to 119 +/- 3 mmHg 5 days after the ANF infusion was initiated, whereas no changes were observed in ANF-infused WKY rats. The SHR had higher plasma levels of both ANF (1-98) and (99-126) than the normotensive controls, but the ANF infusion did not modify these values in either group. Diuresis, natriuresis and haematocrit remained unchanged during the infusion. The higher plasma ANF levels noted in the SHR were associated with a decreased density (Bmax) and enhanced affinity (Kd) of ANF-binding sites in the mesenteric vessels. This pattern was not modified by the ANF infusion. The hypertensive animals had glomerular ANF receptors with a higher affinity than the WKY rats. The Bmax of these receptors was decreased significantly in ANF-infused SHR and WKY rats compared with non-infused animals. We conclude that the lack of change in vascular ANF receptors, during chronic ANF infusion in the SHR, could be associated with the hypotensive response.

Animals↗

PubMedDate not supplied

Prolonged myocardial contrast echocardiography via peripheral venous administration of QW3600 injection (EchoGen): its efficacy and side effects.

We examined the efficacy and side effects of a newly developed contrast agent for intravenous myocardial contrast echocardiography, QW3600 Injection (EchoGen; Sonus Pharmaceuticals, Bothell, Wash.). Doses of 0.1, 0.2, 0.5, and 0.8 ml/kg of this agent were administered intravenously to 8 open-chested dogs. The left ventricular (LV) myocardium was uniformly well opacified for the 0.5 and 0.8 ml/kg doses, for which the peak intensity was an average of 40 gray levels above the baseline intensity. The myocardial opacification persisted even after the contrast echo intensity in the LV cavity had decreased. After ligation of the coronary artery, the area at risk was clearly delineated by the same doses. The agent emulsion and dissolved bubbles were examined microscopically in vitro and in vivo to elucidate the mechanism of prolonged opacification. A microscopic investigation of the mesenteric vessels of a rat indicated that bubbles had formed, growing as large as 30 to 50 microm [corrected] in diameter. The hemodynamic parameters did not change at low doses (0.1 and 0.2 ml/kg), but the systemic pressure fell and the arterial blood oxygen saturation decreased at high doses (0.5 and 0.8 ml/kg). EchoGen provides prolonged contrast for myocardial contrast echocardiography via peripheral venous administration, although the hemodynamic parameters deteriorate at high doses.

Animals↗

PubMed1997

Xanthine oxidase inhibition prevents mesenteric blood flow deficits after resuscitated hemorrhagic shock by preserving endothelial function.

To determine the contribution of xanthine oxidase-mediated endothelial dysfunction to the blood flow deficits seen in the mesenteric circulation after resuscitated hemorrhagic shock, rats were prepared for intravital microscopic study then bled to 50% of baseline blood pressure for 60 min. Treatment animals received a 50 mg/kg bolus and a 25 mg/kg/hr infusion of the xanthine oxidase inhibitor allopurinol (allo) after shock but before resuscitation with shed blood and an equal volume of Ringer's lactate. A similarly resuscitated group (Std Res) and a nonhemorrhage group served as controls. Endothelial function was quantified at baseline, 30 min (R30), and 90 min (R90) postresuscitation as a change in mesenteric vessel diameter after topical application of acetylcholine (Ach), an endothelial-dependent vasodilator. Resuscitation restored cardiac output and blood pressure in both groups. First-order arteriolar blood flow (A1) remained depressed in the Std Res group but was restored to baseline in the group treated with allo. A1 arterioles demonstrated a 22 and a 27% reduction in ability to dilate to Ach at R30 and R90 after Std Res. V1 venules demonstrated a 39 and a 36% reduction in ability to dilate to Ach at R30 and R90 after Std Res. Endothelial-dependent vasodilation and blood flow were preserved in the group receiving Std Res plus allo. The preservation of endothelial function correlated with the restoration of microvascular blood flow postresuscitation. These data suggest that xanthine oxidase-mediated ischemia-reperfusion injury contributes to endothelial dysfunction and blood flow deficits in the mesenteric microcirculation after resuscitated hemorrhagic shock, the effect of which can be attenuated by the addition of the xanthine oxidase inhibitor allopurinol to standard resuscitation.

Acetylcholine↗

PubMedDate not supplied

The insulin-mediated vascular and blood pressure responses are suppressed in CGRP-deficient normal and diabetic rats.

BACKGROUND: Calcitonin gene-related peptide (CGRP) is extensively localized in the perivascular or periadventitia nerves throughout the body. CGRP is a potent vasodilator and its release is associated with dilation of these blood vessels. The present study investigated the contribution of the CGRP-mediated vasodilation to the insulin-induced vasodilatory response. METHODS: Male Wistar rats were treated with capsaicin (50 mg/kg) at 1-3 days of age to ablate the CGRP-containing neurons. After 8 weeks some animals were made diabetic using streptozotocin. Vehicle-treated animals were used as controls. At 12-13 weeks the animals were fasted, anesthetized with chloralose/urethane and instrumented for recording of cardiovascular dynamics. RESULTS: Body weights and basal, insulin, glucose, mean arterial pressure (MAP), heart rate (HR), and vascular flows were not different in CGRP-deficient rats versus controls. Insulin infusion significantly decreased the MAP in vehicle-treated controls but this response was completely attenuated in CGRP-deficient rats. The decreased response to insulin was associated with a diminished vascular dilatory response in the iliac, renal, and superior mesenteric vessel beds. When insulin was infused in CGRP-deficient diabetic animals there was also a diminished response. Diabetes resulted in an increased renal vascular flow in response to insulin. CONCLUSIONS: From the present studies we conclude that the insulin-mediated vasodilation was due, in part, to the stimulation of perivascular nerves to release CGRP, and the action of CGRP on vascular smooth muscle enhanced directly or indirectly the vasodilatory response to insulin.

Animals↗

PubMed1996

Insulin-like growth factor-I decreases mean blood pressure and selectively increases regional blood flow in normal rats.

The insulin-like growth factor-I (IGF-I) and its receptors are widely distributed in peripheral vascular tissue, yet their role in the regulation of blood pressure and blood flow remains unknown. This study investigated the effect of IGF-I on blood pressure and selected regional blood flow in normal Wistar rats anesthetized with chloralose/urethane. The femoral artery was cannulated and used to monitor arterial blood pressure. Electromagnetic flow probes were placed around the left common iliac artery, left renal artery, and the superior mesenteric artery, and used to measure blood flow. IGF-I (2.6 micrograms, 5.1 or 10.3 nmol/animal Iv) was injected as a bolus into the femoral vein. Following the injection of IGF-I (10.3 nmol), we observed a significant decrease of plasma glucose (57%) and a significant decrease of mean arterial pressure (MAP) that continued to decline throughout the 60-min experimental period. IGF-I (5.1 nmol) significantly decreased blood glucose by 44% and decreased the MAP by 14% with a nadir at 15 min and recovery after 60 min. A smaller dose of IGF-I (2.6 nmol) did not significantly decrease the blood glucose but resulted in a slight but significant decrease in MAP. The heart rate was increased by 10.3 and 5.1 but not 2.5 nmol of IGF-I. IGF-I (10.3 nmol) was associated with regional vascular responses with a preferential increase in flow of the iliac and superior mesenteric vessels, measured as vascular conductance. IGF-I (5.1 and 2.6 nmol) increased preferentially renal vascular conductance. Preinfusion with L-NAME, a nitric oxide inhibitor, inhibited the effects of IGF-I on flow. We conclude that IGF-I can selectively dilate vascular beds leading to a decrease in blood pressure and that the response to IGF-I is mediated by nitric oxide.

Animals↗

PubMed1984

Intestinal infarction in rheumatoid arthritis. Three cases due to unusual obliterative vascular lesions.

During a ten-year period, we observed three patients with complicated rheumatoid arthritis (RA) and bowel infarction in which the distal mesenteric vessels were occluded by proliferative endarteritis characterized by intimal proliferation, without vessel wall necrosis or inflammation. Proliferative endarteritis was originally described in patients with RA and digital infarcts and has only rarely been noted in patients with visceral infarcts. Our three patients' pathologic features suggested that these vascular lesions were progressive and rendered patients vulnerable to bowel infarction during periods of decreased cardiac output. Two of the three patients had intestinal infarction without clinical or pathologic evidence of systemic vasculitis. Proliferative endarteritis of visceral arteries rarely causes morbidity and mortality in patients with RA.

Adult↗

PubMedDate not supplied

Spiral CT demonstration of hypervascularity in Crohn disease: "vascular jejunization of the ileum" or the "comb sign".

OBJECTIVE: To report spiral CT imaging features of the vascular alterations observed in active, early, or recurrent Crohn disease of the small bowel and colon. METHODS: Spiral CT examinations of the abdomen and pelvis following oral and intravenous contrast were performed in two cases of active Crohn disease. RESULTS: Spiral CT features of hypervascularity involving the mesenteric vessels of affected segments of bowel include vascular dilatation, tortuosity, and conspicuous prominence and wide spacing of the vasa recta (the "comb" sign). This is attributed to the factors of increased flow and the fibrofatty proliferation in the mesentery and serosa of the affected bowel. CONCLUSION: Clinical application of these observations may enhance the diagnosis of Crohn disease presenting initially or as an acute recurrence in the differential diagnosis from other conditions.

Adult↗

PubMed2006

Cyclooxygenase-1 is involved in endothelial dysfunction of mesenteric small arteries from angiotensin II-infused mice.

Angiotensin II induces endothelial dysfunction by reducing NO availability and increasing reactive oxygen species. We assessed whether cyclooxygenase (COX)-1 or COX-2 participate in the angiotensin II-induced endothelial dysfunction in murine mesenteric small arteries and examined the role of reduced nicotinamide-adenine dinucleotide phosphate-dependent reactive oxygen species production. Mice received angiotensin II (600 ng/kg per minute, SC), saline (controls), angiotensin II + apocynin (reduced nicotinamide-adenine dinucleotide phosphate oxidase inhibitor, 2.5 mg/day), or apocynin alone for 2 weeks. Endothelial function of mesenteric arteries was assessed by pressurized myograph. In controls, acetylcholine-induced relaxation was inhibited by NG-monomethyl-L-arginine and unaffected by DFU (COX-2 inhibitor), SC-560 (COX-1 inhibitor), or ascorbic acid. In angiotensin II-infused animals, the attenuated response to acetylcholine was less sensitive to NG-monomethyl-L-arginine, unaffected by DFU, and enhanced by SC-560 and, similarly, by SQ-29548, a thromboxane-prostanoid receptor antagonist. Moreover, response to acetylcholine was unchanged by ozagrel, a thromboxane synthase inhibitor, and normalized by ascorbic acid. Apocynin prevented the angiotensin II-induced vascular dysfunctions. In angiotensin II-infused mice, RT-PCR analysis showed a significant COX-2 downregulation, whereas COX-1 expression was upregulated. These changes were unaffected by apocynin. Modulation of COX isoform by angiotensin II was also documented by immunohistochemistry. In small mesenteric vessels, the reduced NO availability and oxidant excess, which characterize endothelial dysfunction secondary to angiotensin II, are associated with a reduced COX-2 and an increased COX-1 function and expression. Angiotensin II causes an oxidative stress-independent COX-1 overexpression, whereas angiotensin II-mediated oxidant excess production stimulates COX-1 activity to produce a contracting prostanoid endowed with agonist activity on thromboxane-prostanoid receptors.

Angiotensin II↗

PubMed1986

A mouse model for the study of necrotizing enterocolitis.

A mouse model for the study of necrotizing enterocolitis is presented. It is a model of temporary intestinal ischemia and consists of occluding both superior mesenteric vessels with a bulldog clamp for varying periods of time. The resultant lesions resemble the intestinal lesions seen in necrotizing enterocolitis in respect to the gradual development of the necrotizing lesions and their patchy distribution. We also studied the effect of intravenous saline and low molecular weight dextran in preventing the development of these ischemic lesions. In moderate ischemia, saline and dextran show a similar protective effect, and in severe ischemia, both show a protective effect, with dextran being more effective than saline.

Animals↗

PubMed1985

The effects of indomethacin and PGE2 on vascular reactivity in spontaneously hypertensive rats: possible role of prostaglandins in the pathogenesis of hypertension.

Vascular reactivity was investigated in isolated perfused mesenteric vessels of young and adult SHR and age matched WKY. The primary objective was to investigate whether the difference in vascular reactivity between SHR and WKY would persist if endogenous prostaglandin synthesis was abolished and vascular reactivity restored with fixed exogenous quantities of PGE2. In young rats, when similar concentrations of PGE2 are infused in indomethacin blocked preparations, the difference in vascular reactivity between SHR and WKY is abolished. However, in adult rats the difference persists. It is concluded that enhanced prostaglandin synthesis in hypertension may participate in enhancing vascular reactivity.

Aging↗

PubMed1988

Alpha and beta adrenoceptor blocking action of carvedilol in the canine mesenteric artery and vein.

We observed the effects of carvedilol, a novel beta adrenoceptor blocker, on electrical responses of smooth muscle cells produced by endogenous and exogenous norepinephrine (NE) in isolated canine mesenteric artery and vein. Carvedilol inhibited the NE-induced depolarization in the artery but not in vein, with potencies equivalent to prazosin, i.e., carvedilol blocked alpha 1 adrenoceptors in arterial smooth muscles. Stimulation of perivascular nerves evoked an excitatory junction potential (e.j.p.) and a slow depolarization in these vascular smooth muscles. Carvedilol inhibited the slow depolarization evoked in the artery but not in the vein, with no marked inhibition of the e.j.p.s. High concentrations (10(-5) M) of carvedilol inhibited the e.j.p., slow depolarization, and also the compound action potentials of sympathetic nerve bundles running along the mesenteric vessels, suggesting that these inhibitions were due to local anesthetic actions. The e.j.p. amplitude was increased by isoprenaline and was decreased by NE. The NE and isoprenaline actions were antagonized by yohimbine and propranolol, respectively. Carvedilol inhibited the isoprenaline-actions but not the NE actions on the e.j.p., suggesting that this drug blocked prejunctional beta adrenoceptors but not the alpha 2 adrenoceptors. These results indicate that carvedilol blocks alpha 1 and beta adrenoceptors but not alpha 2 adrenoceptors in vascular tissues.

Action Potentials↗