Our understanding of the regulation of vascular tone has been extended since the identification of vasoactive agents such as the atrial natriuretic peptides, endothelial-derived relaxing factor and endothelin. Unidentified vasopressive agents have been found in platelets. Here we isolate these vasopressors and identify them as diadenosine pentaphosphate (AP5A) and diadenosine hexaphosphate (AP6A) by chromatography, mass spectrometry, ultraviolet spectroscopy and enzymatic cleavage. In the vasculature of isolated perfused rat kidney, both diadenosine phosphates were active at a concentration of 10(-9) M; in aortic rings, contractions were elicited at 10(-8) M. Intra-aortic injection in the rat caused a prolonged increase in blood pressure. We conclude that AP5A and AP6A may play a part in local vasoregulation and possibly in the regulation of blood pressure.

Compliance is an important property of the arterial system and abnormalities in compliance can greatly affect cardiovascular function. The elastic properties of the common carotid artery were therefore studied in 24 normotensive hemodialysis patients and 24 healthy normotensives using a noninvasive technique. The hemodialysis patients and the control subjects were matched for blood pressure. Arterial distension was measured by Doppler analysis of the vessel wall movements and blood pressure was recorded by finger-phlethysmography (Finapres). The vessel wall distensibility (DC: 2.49 +/- 0.23 10(-3)/mm Hg; mean +/- SEM) was significantly reduced and the end diastolic diameter (d: 7.3 +/- 0.3 mm) was significantly increased in younger hemodialysis patients (36.3 +/- 2.0 years) when compared with age-related controls (DC: 3.44 +/- 0.24 10(-3)/mm Hg; d: 6.3 +/- 0.3 mm; mean +/- SEM). In older hemodialysis patients (60.2 +/- 2.3 years), there was no significant difference in vessel wall distensibility (DC: 1.55 +/- 0.15 10(-3)/mm Hg) and vessel diameter (d: 7.8 +/- 0.3 mm) as compared with age-matched controls (DC: 1.77 +/- 0.14 10(-3)/mm Hg; d: 7.2 +/- 0.3 mm). The results show that vessel wall distensibility of the common carotid artery is decreased in younger hemodialysis patients as compared with age-matched healthy subjects. The volume expanded state in hemodialysis patients cannot account for the decreased arterial distensibility, since volume depletion by hemodialysis was not associated with a significant change of arterial distensibility (DC 2.14 +/- 0.44 10(-3)/mm Hg before, DC 2.26 +/- 0.45 10(-3)/mm Hg after ultrafiltration, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Short term enlimomab induction therapy after renal transplantation did not reduce the rate of acute rejection or DGF.

Long-term prognosis in kidney transplant recipients depends on multiple factors. To investigate whether mild proteinuria within the first 6 months following transplantation is a determinant of the long-term function and survival of kidney transplants, 357 patients transplanted between 1980 and 1990 were retrospectively examined over a period of 5 years. 25.5% of the patients developed an early proteinuria between 0.25 and 1.0 g/day over 6 or more months. This group was well matched concerning gender, age of recipient, underlying disease, time on hemodialysis, donor age, cold ischemia time and HLA mismatches with the group without proteinuria (n = 266). Five-year transplant survival in the group with proteinuria was 58.9% in contrast to 85.6% in recipients without proteinuria. Intermittent proteinuria did not worsen long-term prognosis. Proteinuria of 12 months or longer further reduced 5-year transplant survival to 42.6%. Over the whole observation period, serum creatinine in recipients with proteinuria was about 0.5 mg/dl higher as compared with patients without proteinuria. No correlation between proteinuria and gender, age of recipient, duration of hemodialysis, age of donor, cold ischemia time and mismatches could be detected. In conclusion, early proteinuria apparently is not due to established donor or recipient factors. However, there is a strong correlation of proteinuria with worse transplant function and survival.

Apart from lowering blood pressure, antihypertensive drugs may influence vessel wall function. In a randomized double-blind study, the effect of lisinopril and metoprolol on arterial distensibility was studied in 40 patients with essential hypertension. After a placebo run-in period, the patients were randomly treated with metoprolol (50, 100, or 200 mg) or lisinopril (5, 10, or 20 mg) for 10 weeks. In the lisinopril group, blood pressure decreased after 10 weeks of therapy from 173±10/102±5 to 155±10/85±3 mm Hg and in the metoprolol group from 167±12/102±4 to 153±8/84±3 mm Hg. Diameter (millimeters), relative change in diameter (percent), and distensibility (10~3/kPa) of the left common carotid artery were determined after the placebo run-in period and after 6 and 10 weeks of antihypertensive therapy. A multigate Doppler system was used to measure the vessel wall movements by Doppler analysis in M-mode; blood pressure was recorded by finger plethysmography (Finapres). Neither lisinopril nor metoprolol influenced the end-diastolic diameter of the common carotid artery after 6 and 10 weeks of treatment. In the lisinopril group, a significant increase of percent change in diameter (P<.05 compared with the baseline value; P<.05 compared with the metoprolol group) and distensibility (P<.01 compared with the baseline value; P<.05 compared with the metoprolol group) was observed. The results show that lisinopril but not metoprolol improves arterial distensibility in essential hypertension. Pressure-independent effects of angiotensin converting enzyme inhibitors may be important modulators of adaptive changes in the arterial wall. 12 Therefore, pressure-independent changes of arterial distensibility during antihypertensive treatment may reflect changes in medial mass. Interestingly, drugs reducing cardiac hypertrophy similarly improve arterial distensibility, suggesting similar effects on both myocardial and vascular growth stimuli.3 The ominous prognostic significance of cardiac hypertrophy has been clearly defined. Vascular hypertrophy also may adversely affect the course of hypertension. convincingly demonstrated that medial hypertrophy perpetuates a vicious cycle in the development of hypertension. Therefore, the pressure-independent effects on vascular smooth muscle function and growth may attract increasing attention in the evaluation of antihypertensive drugs. In the present study, mechanical properties of the arterial wall were assessed during treatment with the angiotensin converting enzyme (ACE) inhibitor lisinopril and the /3-blocker metoprolol. Despite similar antihypertensive effects, both drugs differed considerably in theneffects on arterial wall properties. MethodsIn a randomized double-blind study, we investigated the effect of antihypertensive therapy with metoprolol and lisinopril on arterial distensibility in 40 patients with untreated essential hypertension. The study was approved by the local From Medizinische Poliklinik, University of Munster, Germany (M.B., C.S., W.Z., K.-H.R.), and the...

To investigate the effect of vascular smooth muscle contraction on mechanical vessel wall properties of proximal "elastic" arteries, we investigated the effect of the vasoconstrictor ergotamine on the distensibility of the common carotid artery in 10 migraine patients with ergotamine intake, in 10 control patients with migraine headache but no prior ergotamine intake, and in 10 healthy control subjects. The patients and control subjects were matched for age, blood pressure, and sex. In the ergotamine group, 2.2 +/- 1.4 mg ergotamine tartrate (0.25 to 6 mg) was taken within 12 hours before investigation. Differences in mean 24-hour blood pressure between the study groups were excluded by 24-hour blood pressure recording and differences in arterial wall thickness by high-resolution and differences in arterial wall thickness by high-resolution B-mode ultrasound. A multigate Doppler system was used for measurement of vessel wall movements by M-mode Doppler analysis. Blood pressure was determined by sphygmomanometry. The end-diastolic diameter of the common carotid artery was insignificantly reduced in the ergotamine group compared with the healthy control subjects and control patients (healthy control subjects, 6.6 +/- 0.4 mm; control patients, 6.7 +/- 0.5 mm; patients with ergotamine intake, 6.3 +/- 0.4 mm; P = NS). Arterial distensibility was significantly lower in the patients with ergotamine intake (17.4 +/- 4.0 10(-3)/kPa) than in the healthy control subjects (22.3 +/- 5.1 10(-3)/kPa) and control patients (22.8 +/- 3.6 10(-3)/kPa) (one-way ANOVA, P = .014). The results show that ergotamine reduces the distensibility of the common carotid artery. The data suggest that vascular smooth muscle contraction can modulate the buffering function of the arterial system independently of blood pressure changes.

Circadian rhythm of blood pressure and of heart rate was studied in patients with hyperthyroidism (n = 10), pheochromocytoma (n = 8), primary hyperaldosteronism (n = 7), and in a control group of essential hypertensive patients (n = 18) and of normotensive healthy subjects (n = 11). 24-hour blood pressure was monitored non-invasively using SpaceLabs (SL 90207) with 8-min intervals in the daytime (8 a.m. to 10 p.m.) and 30-min intervals during night-time (10 p.m. to 8 a.m.). To characterize circadian blood pressure rhythm the difference between the mean blood pressure during daytime and that during night-time was calculated. In patients with hyperthyroidism the day-night difference of the systolic and diastolic blood pressure and of the heart rate was significantly reduced when compared to the normotensive control group (p < 0.05). The day-night difference of the systolic and diastolic blood pressure was significantly lower in the group with pheochromocytoma and hyperthyroidism than in the essential hypertensive controls (p < 0.05); the day-night difference of the heart rate was similar. In the patients with primary hyperaldosteronism the day-night differences of the systolic and diastolic blood pressure and of the heart rate was similar to those in essential hypertensive controls. We conclude that endocrine disorders affecting sympathetic activity like pheochromocytoma or hyperthyroidism influence the circadian blood pressure rhythm, whereas the renin-aldosterone-system has no major impact on the diurnal blood pressure variation. The results therefore support the hypothesis that circadian blood pressure variation is mainly mediated by a modulation of the sympathetic tone.

To assess the influence of long-term hemodialysis on arterial compliance, the elastic vessel wall properties of the common carotid artery were determined in 20 normotensive renal transplant recipients (age 44.7 ± 4.1 years) 8-12 weeks after first transplantation and in 10 healthy controls (age 45.9 ± 5.2 years). Arterial distension was measured by using a multigate pulsed Doppler system, blood pressure curve was recorded by fingerplethysmography. 10 patients with a prior long-term hemodialysis of 51 ± 11 months were compared to 10 patients with a prior short hemodialysis of 18 ± 7 months. The patients and controls had been matched in respect of age, sex and blood pressure. In the long and short-term hemodialysis group, the proportion of patients (n = 10) with a history of mild hypertension was similar – mild hypertension for 25 ± 10 months (n = 5) and for 27 ± 9 months (n ≈ 5). In the group with long-term hemodialysis, the cross-sectional compliance and the distensibility coefficient was significantly reduced in comparison to the group with short-term hemodialysis (p < 0.005) and to the control group (p < 0.001). A significant inverse correlation between the hemodialysis period and the distensibility coefficient (r = -0.59; p < 0.005) showed a decrease in arterial compliance with the length of hemodialysis treatment. The results demonstrate that vessel wall elasticity decreases with the length of hemodialysis treatment and is reduced by hemodialysis-dependent factors, which are detached from sustained arterial hypertension. As cause of reduced arterial compliance in long-term hemodialysis hypervolemia, hypercirculation and disturbed calcium-phosphate metabolism is suggested.