Necrotizing soft tissue infections caused by Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis of groups C and G in western Norway.

Streptococcus pyogenes (group A streptococcus, GAS) is a major cause of necrotizing soft tissue infection (NSTI). On rare occasions, other ß-haemolytic streptococci may also cause NSTI, but the significance and nature of these infections has not been thoroughly investigated. In this study, clinical and molecular characteristics of NSTI caused by GAS and ß-haemolytic Streptococcus dysgalactiae subsp. equisimilis of groups C and G (GCS/GGS) in western Norway during 2000-09 are presented. Clinical data were included retrospectively. The bacterial isolates were subsequently emm typed and screened for the presence of genes encoding streptococcal superantigens. Seventy cases were identified, corresponding to a mean annual incidence rate of 1.4 per 100 000. Sixty-one of the cases were associated with GAS, whereas GCS/GGS accounted for the remaining nine cases. The in-hospital case fatality rates of GAS and GCS/GGS disease were 11% and 33%, respectively. The GCS/GGS patients were older, had comorbidities more often and had anatomically more superficial disease than the GAS patients. High age and toxic shock syndrome were associated with mortality. The Laboratory Risk Indicator for Necrotizing Fasciitis laboratory score showed high values (≥6) in only 31 of 67 cases. Among the available 42 GAS isolates, the most predominant emm types were emm1, emm3 and emm4. The virulence gene profiles were strongly correlated to emm type. The number of superantigen genes was low in the four available GCS/GGS isolates. Our findings indicate a high frequency of streptococcal necrotizing fasciitis in our community. GCS/GGS infections contribute to the disease burden, but differ from GAS cases in frequency and predisposing factors.

A comparison of SAPS II and SAPS 3 in a Norwegian intensive care unit population.

BACKGROUND: Simplified Acute Physiology Score (SAPS II) is the most widely used general severity scoring system in European intensive care medicine. Because its performance has been questioned in several external validation studies, SAPS 3 was recently released. To our knowledge, there are no published validation studies of SAPS II or SAPS 3 in the Scandinavian countries. We aimed to evaluate and compare the performance of SAPS II and SAPS 3 in a Norwegian intensive care unit (ICU) population. METHOD: Prospectively collected data from adult patients admitted to two general ICUs at two different hospitals in Norway were used. Probability of mortality was calculated using the SAPS 3 global equation (SAPS 3 G), the SAPS 3 Northern European equation (SAPS 3 NE), and the original SAPS II equation. Performance was assessed by the standardized mortality ratio (SMR), area under receiving operating characteristic, and the Hosmer and Lemeshow goodness-of-fit C test. RESULTS: One thousand eight hundred and sixty-two patients were included after excluding readmissions, and patients who were admitted after coronary surgery or burns. The SMRs were SAPS 3 G 0.71 (0.65, 0.78), SAPS 3 NE 0.74 (0.68, 0.81), and SAPS II 0.82 (0.75, 0.91). Discrimination was good in all systems. Only the SAPS 3 equations displayed satisfactory calibration, as measured by the Hosmer-Lemeshow test. CONCLUSION: The performance of SAPS 3 was satisfactory, but not markedly better than SAPS II. Both systems considerably overestimated mortality and exhibited good discrimination, but only the SAPS 3 equations showed satisfactory calibration. Customization of these equations based on a larger cohort is recommended.

The effect of tracheostomy on outcome in intensive care unit patients.

BACKGROUND: Percutaneous dilatation tracheostomy (PDT) is increasingly being used in the intensive care unit (ICU), and has probably increased the number of procedures performed. The primary aim of this study was to document the short- and long-term outcome of patients with a tracheostomy performed during an ICU stay. METHODS: Patients in our ICU who underwent an unplanned tracheostomy between 1997 and 2003 were included in this analysis. The type of tracheostomy (PDT or surgical tracheostomy) and time of the procedure were registered prospectively in our ICU database. Survival was followed using the People's Registry of Norway and morbidity data from the individual hospital record. These patients were also compared with a group of ICU patients ventilated for more than 24 h, but managed without a tracheostomy. We also compared patients who had early tracheostomy (less than median time to procedure) with those who had late tracheostomy. RESULTS: Of the 2844 admissions (2581 patients), unplanned tracheostomy was performed during 461 admissions (16.2%) on 454 patients (17.6%). The median time to tracheostomy was 6 days. The ICU, hospital and 1-year mortality rates were 10.8, 27.1 and 37.2%, respectively, significantly less than those of the group ventilated without tracheostomy. The median time to decannulation was 14 days. Patients who had early tracheostomy had a more favourable long-term survival than those who had late tracheostomy. No procedure-related mortality was registered. CONCLUSIONS: In our ICU, having a tracheostomy performed was associated with a favourable long-term outcome with regard to survival, and early tracheostomy improved survival in addition to consuming less ICU resources.

Incidence and mortality after acute respiratory failure and acute respiratory distress syndrome in Sweden, Denmark, and Iceland. The ARF Study Group.

To determine the incidence and 90-d mortality of acute respiratory failure (ARF), acute lung injury (ALI), and the acute respiratory distress syndrome (ARDS), we carried out an 8-wk prospective cohort study in Sweden, Denmark, and Iceland. All intensive care unit (ICU) admissions (n = 13,346) >/= 15 yr of age were assessed between October 6th and November 30th, 1997 in 132 of 150 ICUs with resources to treat patients with intubation and mechanical ventilation (I + MV) >/= 24 h. ARF was defined as I + MV >/= 24 h. ALI and ARDS were defined using criteria recommended by the American-European Consensus Conference on ARDS. Calculation to correct the incidence for unidentified subjects from nonparticipating ICUs was made. No correction for in- or out-migration from the study area was possible. The population in the three countries >/= 15 yr of age was 11.74 million. One thousand two hundred thirty-one ARF patients were included, 287 ALI and 221 ARDS patients were identified. The incidences were for ARF 77.6, for ALI 17.9, and for ARDS 13.5 patients per 100,000/yr. Ninety-day mortality was 41.0% for ARF, including ALI and ARDS patients, 42.2% for ALI not fulfilling ARDS criteria, and 41.2% for ARDS.

Improved oxygenation using the prone position in patients with ARDS.

BACKGROUND: The prone position is known to increase oxygen uptake in patients with Adult Respiratory Distress Syndrome (ARDS). METHODS: In this clinical study from 1995-96, 14 ARDS patients with severe respiratory failure were treated for at least 1 h in the prone position. Responders, defined as having more than 10% increase in PaO2/FiO2 ratio from baseline after 1 h, were treated at least 6 h in the prone position. RESULTS: 11 patients responded during the first period of the prone position (primary responders). Two of the 3 non-responders were turned prone a second time with increase in the PaO2/FiO2 ratio (secondary responders). Mean PaO2/FiO2 ratio (mean +/- SEM) in the supine position was 11.7 +/- 0.8 kPa, increasing to 16.6 +/- 1.8 kPa and 18.0 +/- 1.4 kPa after 1 and 6 h respectively (P = 0.009). Mean time spent in the prone position was 69 h (range 3-256 h), and mean ventilatory time was 17 d (3-52 d). The mortality in this subgroup of our patients with ARDS was 42%, compared to 58% in 19 patients not turned prone in the same period. CONCLUSION: The prone position together with PEEP appears to improve ventilation-perfusion matching. The prone position is simple, effective and readily available and could be used early in most patients with ARDS.

Pulmonary function in adult survivors of severe acute lung injury treated with inhaled nitric oxide.

BACKGROUND: Following an episode of acute respiratory distress syndrome (ARDS), some degree of measurable pulmonary impairment may be anticipated. ARDS is thought to be the more severe form of acute lung injury (ALI) and a recently proposed addition to conventional therapy in ALI/ARDS is inhaled nitric oxide (INO). We carried out a non-randomised follow-up study with pulmonary function tests on survivors of severe ALI/ARDS treated with INO. METHODS: Sixteen previously healthy pulmonary patients, survivors of severe ALI/ARDS, were evaluated with pulmonary function tests >8 months after the acute event. The tests included static and dynamic spirometry, diffusion capacity for carbon monoxide (DLCO), blood gas analysis and evaluation of a chest radiograph. RESULTS: The most common abnormality seen was a low DLCO in 69% of the patients. Abnormally low values were seen in forced vital capacity in 31%, in forced expiratory volume in 1 s in 13%, and in residual volume and total lung capacity in 6%. Blood gas data were within normal limits in 15/16 patients. All chest radiographs showed resolution of the interstitial and alveolar changes present during the acute event. CONCLUSION: In this non-randomised follow-up study we conclude that a degree of measurable pulmonary impairment after INO treatment in severe ALI/ARDS was common, but did not differ markedly from other published studies on pulmonary function in similar patient material. No late unexpected major abnormalities due to the inhaled nitric oxide treatment could be identified in these survivors.

Relaxing effects of cyclic GMP and cyclic AMP-enhancing agents on the long-lasting contraction to endothelin-1 in the porcine coronary artery.

In the coronary circulation, endothelin-1 (ET-1) evokes spasms which are difficult to treat when the endothelial integrity is compromised. This study compares several classes of relaxing agents on already established contractions to ET-1 in an in vitro model using ring segments of the porcine left descending coronary artery (pLAD). All segments were precontracted with 10 nmol/L ET-1. The calcium channel blocker isradipine was 300 times more potent than verapamil, but was only a partial relaxant; the maximal relaxation obtained was 52 +/- 2% (n = 6). Atrial natriuretic peptide (ANP) was an equally potent relaxant of the ET-1 contraction; however, it too was an incomplete relaxant, maximal relaxation being < 60%. A 50% relaxation of the ET-1 contraction was obtained with 0.28 +/- 0.24 mumol/L ANP, n = 4 (IC50). Comparison of cyclic nucleotide analogues revealed a 30 times higher potency for 8-bromo-cyclic guanosine monophosphate (8-Br-cGMP)(IC50 44 +/- 11 mumol/L, n = 6) than for 8-bromo-cyclic adenosine monophosphate (8-Bi-cAMP) (IC50 1600 mumol/L, n = 6). The cyclic nucleotide phosphodiesterase (PDE) inhibitor milrinone, a PDE 3-inhibitor with an IC50 2.4 +/- 1.8 mumol/L, (n = 6) was 10 times more potent than rolipram (PDE 4-inhibitor), zaprinast (PDE 5-inhibitor) and vinpocentine (PDE 1-inhibitor). Withdrawal of these analogues and inhibitors from segments continuously exposed to 10 nmol/l ET-1 revealed that vinpocentine and 8-Br-cGMP were irreversible relaxants, in contrast to milrinone and 8-Br-cAMP. In conclusion, this study has demonstrated that cGMP-enhancing agents, such as the naturally occurring ANP, the calcium channel blocker isradipine, and the synthetic inhibitor of PDE 3, were the most effective relaxants of ET-1 evoked contractions in pLAD in vitro.

A retrospective analysis of nitric oxide inhalation in patients with severe acute lung injury in Sweden and Norway 1991-1994.

BACKGROUND: Patients with severe acute lung injury (ALI) have been treated compassionately on doctors' initiative with inhaled nitric oxide (INO) in Sweden and Norway since 1991. In 1994 the previously used technical grade nitric oxide was replaced by medical grade nitric oxide. METHODS: We have carried out a retrospective data collection on all identified adult patients treated with INO for >4 h during the period 1991-1994 focusing on safety aspects and patient outcome. We used the following exclusion criteria (1) Age <18 years, (2) Simultaneous treatment with extracorporeal removal of CO2 (3) NO inhalation period <4 h, (4) Incomplete or missing patient charts, (5) Use of INO in order to treat pulmonary hypertension following cardiac surgery, with little or no acute lung injury. RESULTS: Inclusion criteria were met by 56 out of 73 identified patients. Mean age was 48+/-19 years and the median duration of INO treatment was 102 h. PaO2/FIO2 ratio at start of treatment was 85 +/- 33 mm Hg with a lung injury score (LIS) of 3.2+/-0.8. The aetiology of the lung injury was pneumonia (n= 27), sepsis (n=12) and trauma (n=8). Survival to hospital discharge was 41% and survival after 180 d was 38%. Three serious adverse events were identified, two from technical failures of the INO delivery device and one withdrawal reaction necessitating slow weaning from INO. No methaemoglobin values >5% were reported during treatment. CONCLUSION: The overall mortality did not differ dramatically from historical controls with high mortality. Only a randomised study may determine whether INO as an adjunct to treatment alters the outcome in severe ALI. One cannot at present advocate the routine use of INO in patients with ALI outside such studies.

Human pheochromocytoma: different patterns of catecholamines and chromogranins in the intact tumour, urine and serum in clinically unsuspected cases.

Clinically unsuspected pheochromocytoma is usually discovered either at autopsy or during surgical intervention for unrelated conditions, despite often enormous neoplastic masses producing and storing catecholamine (CA). In order to assess whether these tumours share some common features we have compiled data for six patients admitted to hospital without previous diagnosis of their pheochromocytoma. The clinical variables and the morphological and immunohistochemical characteristics of the tumours revealed that these cases represented quite different expressions of adrenomedullary neoplasms. They differed not only with respect to nuclear ploidity and overall cytoplasmic morphology but also in catecholamine storage and expression of immunoreactive chromogranin A sequences in the intact tissue. In two of the patients hypertension had been overlooked as a diagnostic indicator of their CA-producing tumours. There was no clear relationship between the mean arterial pressure, the tumour content of CA and the serum levels of CA. Processed chromogranin A dominated in the serum of the two hypertensive cases. The 24-h urine values of CA and its main metabolite (vanillin mandelic acid) were, together with the serum values of chromogranin A and B, proportional to tumour mass and provided the most reliable diagnostic indicators for the non-hypertensive as well as the hypertensive cases.

[Nitrogen oxide (nitrogen monoxide) administered via respirator. A new therapeutic alternative in acute respiratory failure and shock lung]. / Nitrogenoksid (nitrogenmonoksid) tilført via respirator. Et nytt behandlingstilbud ved akutt lungesvikt og sjokklunge.

Adult respiratory distress syndrome (ARDS) still has a high rate of mortality. It is usually necessary to treat these patients with a respirator using a high inspiratory fraction of oxygen. The condition is often associated with pulmonary hypertension and increased pulmonary vascular resistance. Nitric oxide (NO) has been shown to be a potent endogenous vasodilator. It is a gas and can thus be delivered to the lungs of intubated patients by means of a respirator. Because of its very short halflife, the effect of inhaled nitric oxide is limited to the pulmonary vasculature and it has no systemic effects. The local vasodilatation caused by nitric oxide leads to improved oxygenation, primarily because of reduced intrapulmonary shunting of blood. From April 1993 to July 1995 we treated 14 patients with severe ARDS with inhaled nitric oxide. All patients were critically ill, with a mean APACHE II score of 24.5. Oxygenation was increased in all patients after treatment with nitric oxide, but in spite of this eight patients (56%) died. There were no significant differences between survivors and non-survivors as regards age or severity of the disease.

Surgery during inhalation with nitric oxide in a patient with severe adult respiratory distress syndrome (ARDS).

Nitric oxide (NO) is increasingly used in intensive care units (ICU) in order to treat serious hypoxaemia secondary to ARDS. Since interrupting NO delivery in such patients for more than a few minutes could lead to serious adverse events, moving the patient outside the ICU has been very difficult. Recently developed equipment (Noresc 1503) enabled us to deliver 10 or 20 ppm NO from a ventilatory bag with reservoir. This is used for ventilation under transport from the ICU to the operating theatre (OT) or radiology department. We present a patient with severe ARDS undergoing major surgery while being treated with NO. The patient could be moved to the OT and operated on during five hours without significant changes in vital functions.

Vasoinhibitory activity of synthetic peptides from the amino terminus of chromogranin A.

Naturally occurring amino terminal fragments of chromogranin A (CGA), the calcium-binding protein found in all endocrine secretory vesicles, have vasoinhibitory activity when tested in isolated segments of the endothelium-denuded human saphenous vein. Synthetic peptides corresponding to sequences within the first 76 residues of chromogranin A have been made and tested for biological activity. Full length vasostatin I (CGA1-76) (40 nM), but not the truncated vasostatin I, CGA1-40 (100 nM) mimics natural chromogranin A fragments in its inhibition of contractions induced by endothelin-1 (ET-1) in calcium containing medium. CGA1-40 (100 nM) mimics the inhibitory effect of the vasostatins on the contractions induced in the absence of extracellular calcium by high potassium and noradrenaline, but not by ET-1. The iodinated peptides both exhibit saturable binding in an aortic smooth muscle cell line, indicative of a single class of high affinity binding protein ('receptor' with an apparent KD of approximately 45 nM. This binding is not affected by endothelin-1. Iodinated peptides can be crosslinked to a single polypeptide in binding experiments performed on intact calf aortic smooth muscle cells.

[The physiological and pathophysiological significance of endothelins]. / Endotelinenes fysiologiske og patofysiologiske betydning.

Endothelin-1 (ET-1) is a vasoconstrictor peptide of endothelial origin belonging to a family of four isopeptides consisting of ET-1, ET-2, ET-3, and vasoactive intestinal constrictor also called ET-4. These peptides show considerable homology with the sarafotoxins which are cardiotoxic molecules present in the venom of the snake Israeli burrowing asp. ET-1 is the most potent vasoconstrictor known, ten times more potent than angiotensin II. It is synthesized in response to stress, hypoxia, and other vasoactive substances. The physiological role of the endothelins and site of synthesis for ET-2 and ET-3 are still unknown. Two endothelin receptors have been cloned. Elevated plasma levels of ET-1 have been measured in patients suffering from various diseases such as myocardial infarction, cardiogenic shock, septic shock, renal failure, subarachnoid haemorrhage and pre-eclampsia. ET-receptor antagonists and ET-1 synthesis inhibitors are now available. It has been shown that these inhibitors, and also ET-1 antibodies, ameliorate the consequences of severely impaired blood flow in the kidney and in the brain. In animals, infusion of endothelin antibody has been shown to limit the size of myocardial infarction. ET-1 inhibitors can be expected to play a therapeutic role in the future.

Human chromostatin inhibits endothelin-1-induced contractures in human blood vessels.

Isolated endothelium-denuded segments of the human internal thoracic artery (ITA) and saphenous vein (SV) have been used for characterization of vasoinhibitory effects of the chromostatin (hChs) sequence of human chromogranin A (CGA124-143). In SV preincubation with hChs inhibited the response to depolarizing high K+ in Ca(2+)-free medium in a concentration dependent manner (EC50 approximately 2 nM). At 200 nM hChs the tension response to high K+ (80 mM) was inhibited by 44% (n = 8) and the tension response to noradrenaline (2.6 microM) was inhibited by 20% (n = 6), but the tension response to endothelin-1 (65 nM) (ET-1) was not affected. In ITA no effect of hChs was observed on tension response to K+ or ET-1 in Ca(2+)-free medium. On the other hand, in Ca(2+)-containing medium the tension evoked by 65 nM ET-1 was no longer sustained in segments preincubated with 200 nM hChs and declined spontaneously to 76 +/- 12% (n = 6) of maximal tension after 6 min. A vascular function for the Chs sequence of the human CGA is thus indicated, inhibiting different components of vasoconstrictor responses in the human SV and ITA segments.

Vasostatins, comprising the N-terminal domain of chromogranin A, suppress tension in isolated human blood vessel segments.

Chromogranin A (CGA) belongs to a family of highly acidic proteins which are co-stored and co-released with the catecholamines from the mammalian adrenal gland and occur in nmolar concentrations in the human circulation. A vascular function for the adrenomedullary released and circulating CGA has yet to be established. The present study reports on the novel vasoinhibitory effect of the N-terminal domain of the adrenomedullary CGA in isolated segments of the human internal thoracic artery (ITA) and saphenous vein (SV). The collective term vasostatin(s) refers to N-terminal fragments (CGA1-76 and CGA1-113) of apparent molecular weights 7 to 22 kD, to indicate their vascular inhibitory effects. The sustained contractions evoked by the potent vasoconstrictor peptide, endothelin-1 (ET-1) were suppressed when ITA and SV segments were preincubated for 15 min with vasostatins (72 nM). The vasoinhibitory effects were not dependent on an intact endothelium and suppression of the response to 35 nM ET-1 was approximately 77% and approximately 40% in endothelium-denuded ITA and SV segments, respectively. In endothelium-denuded SV segments the vasostatins suppressed the maximal sustained tension response but not the potency for ET-1, indicating that the vasostatin effect did not involve interference with ET-1 binding to its vascular receptor. Preincubation of endothelium-denuded SV segments with nifedipine (1 microM) inhibited the sustained response to ET-1 > or = 10 nM by 50%.(ABSTRACT TRUNCATED AT 250 WORDS)

The vasoinhibitory activity of bovine chromogranin A fragment (vasostatin) and its independence of extracellular calcium in isolated segments of human blood vessels.

Endothelium-independent vasoconstrictor responses in isolated segments of human internal thoracic artery (ITA) and saphenous vein (SV) were used as a bioassay system for the vasoinhibitory activity of bovine chromogranin A (CGA). Preincubation with vasostatin (0.8 micrograms/ml), containing the N-terminal domain of CGA, (CGA1-76, CGA1-113 and CGA1-143ff), inhibited the contractile responses evoked by 80 mM K+, 2.6 microM noradrenaline (NA), or 65 nM endothelin-1 (ET-1) in Ca(2+)-free solution in SV but not in ITA. The results demonstrate a vasoinhibitory activity in vasostatin and show that there is a marked difference between the arterial and venous segments in the Ca2+ independent component of the inhibitory response. A vascular role for the N-terminal domain of CGA is indicated, presumably by inhibiting Ca2+ release from intracellular stores in the human vein but not the artery.

In vitro responses to atrial natriuretic polypeptide in human vessels commonly used as aortocoronary bypass grafts.

Vascular effects of atrial natriuretic polypeptide (APII), i.e. the peptide hormone released from the atrial myocardium, were investigated in segments of the human internal thoracic artery (ITA) and saphenous vein (SV) with intact (+E) or injured (-E) endothelium. All segments were subject to several cycles of agonists in order to detect tachyphylactic or facilitatory responses. Opposite, indirect effects on the noradrenaline contracted ITA and SV were obtained in response to APII at a supranormal concentration (50 nM) which had no direct relaxing action on the isolated segments in vitro. In ITA the noradrenaline contractures in subsequent cycles were reduced to 41 +/- 21% (+E) and 28 +/- 9% (-E), but in SV they were enhanced to 211 +/- 115% (+E) and 483 +/- 242% (-E) of those before APII exposure. Thus under in vitro conditions ITA could be indirectly relaxed by APII via tachyphylactic effect on the noradrenaline contracture. SV, on the other hand, was markedly potentiated by APII in its noradrenaline response. In injured endothelium these opposite effects were aggravated.

Comparative aspects of the endocrine myocardium.

Secretory organelles are common features of the myocardium, from cyclostomes to man, and occur in the atria of all vertebrates, in the ventricle of the lower vertebrates and in the embryonic and foetal ventricles of mammals. These organelles constitute the final step in the regulated secretory pathway for the atrionatriuretic polypeptides collectively termed atriopeptins. At birth, however, the mammalian ventricle shifts to constitutive secretion, with low levels of atriopeptins in the normal and elevated levels in the hypertrophied adult ventricle. In the mammalian atria the atriopeptins are costored with the calcium-binding, highly acidic chromogranins A and B, and the secretory organelles account also for the highest subcellular calcium concentration in the myocardium. These similarities between the myocardium and the neuroendocrine system confirm and extend the earlier observations and point to new aspects of the endocrine heart; as a source of prohormones not only for the atriopeptins but also for members of the chromogranin family. A significant role is also apparent for the secretory organelles in the intracellular sequestration of calcium in both the normal and the overstimulated myocardium. Down-regulation of excess in blood volume appears to be mediated by atriopeptins via indirect and direct relaxations of vascular smooth muscle in the aorta and other large arteries. Apart from their natriuretic actions, the atriopeptins also contribute to substantial fluid loss via the gastrointestinal tract.

Differential patterns of relaxation by synthetic atrial peptide (APII) in the pulmonary artery, ascending and distal abdominal aorta.

The vasodilatory effects of the synthetic rat atriopeptin (APII) have been studied in vitro in agonist-contracted, endothelium-denuded segments of the rat pulmonary artery, the ascending, and the distal abdominal aorta. In the pulmonary artery the contractures to methoxamine were inhibited more potently by APII (pD2 = 9.10 +/- 0.40, n = 6) than by the vasodilatory neuropeptide VIP (pD2 = 7.37 +/- 0.66, n = 6). The intrinsic activity of APII was 0.46 +/- 0.16 (n = 6). In segments previously exposed to either VIP or the beta 2-agonist salbutamol, APII was a near complete agonist (alpha = 0.82 +/- 0.17, n = 7 and 0.84 +/- 0.14, n = 6, respectively) without significant changes in the potencies. APII was a complete agonist also for the inhibition of the alpha-agonist-contracted segments of the aorta, however, with potencies 10-fold lower than in the pulmonary artery. VIP was without functionally significant effects in the aorta. The tachykinins (CGRP, SP, Neurokinins A and B) were without effects in all segments tested. In the ascending aorta, APII induced a long-lasting tachyphylaxis to the alpha-agonists, nearly completely abolishing the subsequent responsiveness to NA and methoxamine for more than 4 h.