[Clinical outcomes of surgical management of acromioclavicular dislocation with and without ligament suturing]. / Klinické výsledky operacního resení acromioclaviculárni luxace se suturou a bez sutury vazu.

INTRODUCTION: The aim of the study was to present a retrospective assessment of clinical outcomes of acromioclavicular (AC) dislocation surgery with and without suturing of the coracoclavicular ligament (CC). MATERIAL AND METHODS: Patients regardless of their age and gender were included in the study. All the subjects were operated by the same surgeon using the same surgical technique--traction cerclage. Every odd-numbered patient's procedure included ligament suturing and every even-numbered patient was operated without ligament suturing. The patients underwent clinical follow up at identical time intervals, had Pruban (elastic net bandage) fixation applied for one week and had the same rehabilitation regime for 6 weeks. The wires were extracted at 6-8 months. A total of 42 patients were included in the study. All the subjects were classified according to Tossy III, based on x-ray findings. The study group included 36 males and 6 females. The average age was 31.8 years (17-55). In 14 cases, preoperative stress x-rays of the upper extremity were performed. CC ligmanet suture was completed in 21 patients and 21 patients underwent procedures without CC suturing. The clinical outcome was assessed after wire extraction. RESULTS: Painful complications were recorded in 2 subjects and they reported the pain to be intermittent. The pain was classified as maximum grade 4, based on VAS (Visual analogue score). In one patient, the authors recorded pain sensation in the area of Kirschner's wires endings. In this particular patient, the wires were extracted 6 weeks after the procedure and following that, the patient was symptom-free. CONCLUSION: Based on the findings, the authors recorded no differences in the clinical outcomes of AC surgery with or without CC ligament suturing.

[Comparative clinical study assessing C2 dens injuries treatment outcomes]. / Klinická komparativní studie výsledku terapie poranení zubu cepovce.

The aim of this restrospective study was to compare treatment outcomes of C2 dens fractures following their conservative or surgical management, using direct osteosynthesis with canalised screws and the Dens Access device. During 1999-2006, 108 patients with type II and type III dens injuries, based on the Anderson-D'Alonzo classification, were treated in the Brno Traumatology Hospital (Urazová nemocnice Brno). Patients with type I injuries were excluded from the study. The study included 32 patients, who presented for a chek-up. Out of the total, 15 patients had undergone surgery, 17 had been managed conservatively. The mean age was 56 years (17-83 y.o.a.), 19 subjects were males and 13 subjects were females. The conservative treatment included the following methods: treatment with a Philadelphia collar (4 subjects) or a halo apparatus (13 subjects). Only patients, in whom at least a year elapsed since their injury, were included in the study. The control group showed inferior results on ROM (range of motion), VAS (Visual analogue scale) and x-ray examinations. Overall, in the conservative group, 3 subjects showed restricted cervical range of motion, compared to a single subject in the operated group. The mean VAS was 3.6 (0-7) in the conservative group, compared to the mean VAS of 2.9 (0-6) in the operated group. No fragment displacements or development of a pseudojoint was recorded in the operated subjects. In the conservative group, fragment displacement was observed in 2 subjects. In the both subjects, the bone healed. The Fisher's exact test and the Mann-Whitney U-test were used for statistical analysis of the data.

Long-term blockade of the angiotensin II receptor in renin transgenic rats, salt-loaded Dahl rats, and stroke-prone spontaneously hypertensive rats.

These studies were designed to investigate the protective effects of the new angiotensin II receptors antagonist BAY 10-6734 (6-n-butyl-4-methoxycarbonyl-2-oxo-1[(2'-(1H-tetrazol-5-yl) -3-fluorobiphenyl-4-yl)methyl] 1,2-dihydropyridine, CAS 156001-18-2) on haemodynamic, hormonal, renal, and structural parameters in renin transgenic rats (TGR(mRen2)27), salt-loaded Dahl S and R rats, and salt-loaded stroke-prone spontaneously hypertensive rats (SHR-SP) in long-term trials. Study 1: In SHR-SP the development of blood pressure, cardiac hypertrophy, and the deleterious effects of salt loading on kidney structure and kidney function was prevented by BAY 10-6734. Study 2: In salt-loaded Dahl S rats with a suppressed plasma renin activity treatment with BAY 10-6734 did not delay the increase in blood pressure but prevented cardiac hypertrophy and the increase in plasma ANP (Atrial natriuretic peptide). Study 3: TGR develop malignant hypertension associated with cardiac hypertrophy, elevated left-ventricular end-diastolic pressure and increased plasma ANP. After 6 weeks of treatment with BAY 10-6734 (30 mg/kg p.o. bid) cardiac pump function was improved and cardiac hypertrophy was reversed in this angiotension dependent form of hypertension. The beneficial effects of BAY 10-6734 in these different animal hypertension models are also emphasized by a reduction in mortality.

Interaction of a neutral endopeptidase inhibitor with an ANP-C receptor ligand in anesthetized dogs.

Inhibition of important degradative pathways of atrial natriuretic peptide (ANP) in vivo could be a valuable therapeutic tool for regulating endogenous levels of ANP. The aim was to investigate the in vivo effects of both blockade of atrial natriuretic peptide clearance receptor and inhibition of neutral endopeptidase 24.11, an enzyme shown to be involved in ANP breakdown. Therefore, we infused a specific neutral endopeptidase inhibitor ((S)-thiorphan) and an ANP-C receptor ligand (AP 811) alone or in combination into anaesthetized beagle dogs. Compared with vehicle controls, coadministration of (S)-thiorphan and AP 811 (100 micrograms/kg/min and 10 micrograms/kg/min, resp.) had greater effects on endocrine and renal parameters than administration of either substance alone. Coadministration of both compounds increased urinary excretion of volume and sodium, cGMP and ANP. We found also increased plasma cGMP, plasma ANP and decreased plasma renin activity. No effects were observed with respect to blood pressure, left ventricular pressure or heart rate during the infusion period of 2 h. We conclude from these investigations, that blocking both degrading pathways of ANP with the ANP-C receptor ligand AP 811 and the neutral endopeptidase inhibitor (S)-thiorphan is more effective than inhibition of either system alone. Such a combination might therefore be a useful therapeutic tool in cardiovascular diseases.

Effect of nifedipine on coronary capillary geometry in normotensive and hypertensive rats.

The aim of this study was to describe quantitatively changes in the coronary capillary network resulting from hypertrophy in spontaneously hypertensive rats (SHR) and a potential effect of long-term treatment of these animals with nifedipine. Age-matched male SHR and Wistar-Kyoto (WKY) rats were treated for 27 weeks. Four experimental groups were analyzed: (1) untreated SHR, (2) nifedipine-treated SHR, (3) untreated control WKY rats, and (4) nifedipine-treated WKY rats. Treatment significantly decreased systolic blood pressure in SHR, although normotensive pressures were not reached. SHR had significantly higher cardiac weight, which decreased in nifedipine-treated rats, but values remained above those in control animals. Morphometric evaluation revealed lower capillary density and larger capillary domain area in hearts from SHR, which were partially attenuated by treatment with nifedipine. Capillary domain area was also significantly larger at arteriolar portions compared with domains supplied at venular portions. Capillary segment length was consistently shorter on the venular than arteriolar portion of the capillary, whereas no differences were observed between hearts from WKY rats and SHR. Treatment with nifedipine resulted in a prolongation of segment length. Reconstruction of the three-dimensional capillary supply unit (capillary domain area times capillary segment length) revealed significant differences between the amount of tissue supplied by a capillary at its arteriolar portion than more distally, which was detectable in all experimental groups. In hypertrophic hearts from SHR this tissue volume is increased mainly because of longer intercapillary distances and larger domains, especially on arteriolar portions.(ABSTRACT TRUNCATED AT 250 WORDS)

Future prospects for calcium antagonists.

In hypertensive disease, calcium antagonists (CA) affect the limiting step of increased vascular resistance. In the future, it is likely that the use of calcium antagonists will be extended to the early stage of hypertension, which is characterised predominantly by preglomerular vasoconstriction and only discrete impairment of renal function. In the advanced stages of hypertension they will be used to prevent vascular remodelling and to limit renal and cardiac tissue damage. By preventing excessive calcium overload, calcium antagonists preserve tissue integrity and reverse the progression of specific vascular pathologies such as arteriosclerosis and microangiopathy through mechanisms independent of their blood pressure-lowering effect. The protective effect demonstrated by nifedipine against toxic and radiation-induced changes in nonvascular tissue in animal models merits specific attention.

Cardiac structural remodelling after treatment of spontaneously hypertensive rats with nifedipine or nisoldipine.

OBJECTIVE: The aim was to determine if long term treatment with nifedipine or nisoldipine affects structural remodelling of cardiac myocytes and is effective in attenuating or preventing reparative and reactive myocardial fibrosis in essential hypertension. METHODS: Five and a half month old male spontaneously hypertensive rats and Wistar Kyoto (WKY) rats received either 1000 ppm nifedipine or nisoldipine or no treatment (controls) for 22 weeks. Haemodynamic variables were measured and hearts recovered from animals of each group. Cardiac myocytes were isolated by retrograde coronary perfusion with collagenase. Cell volume was determined by Coulter analysis, cell length by direct measurement, and cross sectional area by volume/length. Cardiac myocyte number was calculated for both ventricles. Tissue sections from perfusion fixed hearts were stained with picrosirius red and myocardial collagen was analysed. Reparative fibrosis was assessed by the presence of microscopic scarring and reactive (interstitial and perivascular) fibrosis was quantified. RESULTS: Nifedipine and nisoldipine significantly decreased systolic and diastolic blood pressure in spontaneously hypertensive rats, although normotensive pressures did not result. Left ventricular weight relative to body weight was significantly decreased in nifedipine and nisoldipine treated compared with untreated spontaneously hypertensive rats, although values remained significantly greater than WKY controls. Cardiac myocyte volume was slightly decreased with attenuation of blood pressure in spontaneously hypertensive rats, but no significant differences were found. Cardiac myocyte number for each ventricle was similar between groups. Microscopic scarring was significantly decreased in nifedipine and nisoldipine treated compared with untreated spontaneously hypertensive rats and interstitial and perivascular fibrosis were substantially reduced. CONCLUSIONS: Nifedipine and nisoldipine: (a) attenuate hypertension and decrease left ventricular mass in spontaneously hypertensive rats, but the associated decrease in myocyte size was not significant; (b) are cardioprotective as indicated by a significant decrease in the incidence of microscopic scarring; and (c) decrease the extent of reactive, both interstitial and perivascular, fibrosis normally found in untreated spontaneously hypertensive rats. Nifedipine and nisoldipine have the potential to positively alter myocardial pathology in essential hypertension.

Inhibition by atrial natriuretic peptide of endothelin-1-stimulated proliferation of vascular smooth-muscle cells.

The effect of endothelin-1 (ET-1) on proliferation of aortic vascular smooth-muscle cells (VSMCs) from spontaneously hypertensive (SHRs) and normotensive Wistar-Kyoto (WKY) rats was assessed by the measurement of [3H]-thymidine incorporation into DNA. ET-1 stimulated DNA synthesis in a concentration-dependent manner. Half-maximal stimulation occurred at a concentration of 7 x 10(-11) M. Three separate administrations of ET-1 to the cell cultures resulted in a half-maximal stimulation at 3 x 10(-12) M in of VSCMs from SHRs. VSMCs from SHRs responded to a far greater extent compared with WKY rats. The stimulatory effect of ET-1 was significantly attenuated by atrial natriuretic peptide (ANP). Repeated administration of ANP led to exacerbation of the inhibitory effect. Serum-stimulated DNA synthesis was not influenced by ANP. The proliferative action of ET-1 and the inhibition by ANP are discussed with respect to the development of vascular disease in atherosclerosis and hypertension.

Endogenous atrial natriuretic factor is involved in the natriuresis following sodium loading in rats with chronic heart failure.

STUDY OBJECTIVE: Plasma levels of atrial natriuretic factor are increased in chronic heart failure; however, it is still controversial whether these raised levels contribute to the diuresis and natriuresis in this setting. To address this issue the potential contribution of endogenous atrial natriuretic factor in the renal excretion of a moderate oral sodium load in a rat model of chronic heart failure was studied. DESIGN: A monoclonal antibody against atrial natriuretic factor was used for specific antagonisation of its in vivo effects. Animals were subjected to oral sodium loading (30 ml.kg-1 0.9% NaCl, 2.5% dextrose) at baseline, immediately after, and 5 d after injection of monoclonal antibody or control solvent. EXPERIMENTAL MATERIAL: Sham operated rats and rats with chronic heart failure due to myocardial infarction (infarct size 35(SEM 4)% of left ventricle) were studied 4-5 weeks after surgery. MEASUREMENTS AND MAIN RESULTS: The renal excretion of cyclic guanosine monophosphate (cGMP), which represents a specific marker for the activation of the atrial natriuretic factor system, was markedly increased in infarcted rats, at 17.9(SEM 3.4) vs 5.8(1.2) nmol.kg-1, p less than 0.01. Atrial natriuretic factor antibody given immediately before sodium loading reduced the natriuretic response (0-4 h period) in infarcted rats from 1270(171) to 805(76) mumol.kg-1 (p less than 0.01) but not in sham operated animals. Similarly, the excretion of cGMP was only decreased by atrial natriuretic factor antibody in infarcted rats, from 29.8(6.3) to 20.7(3.7) nmol.kg-1. The reduction in sodium and cGMP excretion in infarcted rats was confirmed with a purified antibody preparation. CONCLUSIONS: Endogenous atrial natriuretic factor appears to be involved in the natriuresis following a moderate oral volume load in chronic heart failure. Thus the raised concentrations found in chronic heart failure may contribute to the regulation of urinary sodium excretion under these conditions despite the fact that the diuretic effects of exogenous atrial natriuretic factor are attenuated in chronic heart failure.

Autoradiographic localization of 125I-big endothelin-1 in rat tissues.

Endothelin-1 (ET-1), a potent vasoconstrictor with a characteristically long-acting activity in vitro and in vivo, is thought to be generated in endothelial cells from a less active intermediate, big endothelin-1 (big ET-1). In addition to ET-1, big ET-1 is also present in the circulation. The autoradiographic localization of 125I-big ET-1 has been studied after intravenous administration in rat tissues. Highest enrichment of radioactivity was found in the kidney cortex. Compared to blood levels, enrichment of radioactivity is also detected, especially in the vascular wall of the aorta. Comparing the radioactivity pattern of ET-1 and big ET-1, a nearly identical tissue distribution is observed, with the exception of the relative enrichment in the lung, the endocardium and the zona glomerulosa.

Inhibitory effects of nisoldipine on serotonin and potassium induced contractions of porcine coronary and femoral arteries.

The inhibitory effect of nisoldipine (Baymycard, Syscor; CAS 63675-72-9) and nifedipine on the serotonin and potassium induced contractions of porcine coronary and femoral arteries in vitro has been investigated. Both nisoldipine and nifedipine inhibited preferentially the serotonin induced contraction in the coronary artery being less effective in the inhibition of the femoral artery. The coronary selectivity of nisoldipine is at least 10 times more pronounced than that of nifedipine. The serotonin antagonist ketanserin inhibited contractions on both vessels with the same potency. The potassium induced contraction was inhibited by the dihydropyridines in both coronary and femoral artery. Nisoldipine again, was more potent than nifedipine in the inhibition of coronary artery spasm but not in the contraction of femoral artery. Ketanserin did not inhibit contractions of any vessels.

Effects of a chronic treatment by nisoldipine, a calcium antagonistic dihydropyridine, on arteries of spontaneously hypertensive rats.

Earlier studies have shown that relaxation in response to several agents is impaired in arteries from spontaneously hypertensive rats (SHR). We had previously reported that SHR aortas present a delayed relaxation when first exposed for 35 minutes to a 100 mM KCl solution and then transferred into physiological solution. The first phase of relaxation appeared similar in SHR and Wistar-Kyoto rat arteries, but the second phase was markedly slowed down in SHR arteries, giving rise to a postcontraction tone. In this study, we found that this postcontraction tone could be demonstrated not only in the aorta but also in the mesenteric artery, was independent of the presence of endothelium, increased with the age of SHR, and disappeared progressively when arterial segments were submitted to successive cycles of KCl depolarization followed by reimmersion in physiological solution. Chronic treatment of SHR with nisoldipine at doses that blocked the development of hypertension and attenuated the concomitant hypertrophy of heart and aorta, or in vitro pretreatment of SHR arteries with nisoldipine, decreased the contractile force developed by arteries in response to KCl depolarization and normalized the subsequent relaxation. [3H] (+)-PN200-110 binding studies on heart and brain homogenates indicated an increase in apparent Kd in nisoldipine-fed rats without significant change in Bmax. Binding data were compatible with the view that occupation of dihydropyridine receptors by nisoldipine after chronic oral administration was responsible for the modifications observed ex vivo in the mechanical activity of arteries. We conclude that the postcontraction tone of SHR arteries was mainly due to an abnormally prolonged activation of calcium channels after transfer of depolarized arteries into the physiological solution and that a labile or slowly releasable factor was probably involved in this phenomenon. We suggest that the antihypertensive action of nisoldipine might be related to the mechanisms involved in the suppression of the postcontraction tone as observed in vitro and that this mode of action could be more important than the vasodilating effect of this drug.

Long-term protective effects of nitrendipine in experimental hypertension.

The antihypertensive and tissue-protective effects of nitrendipine were studied after long-term treatment of rats with experimental hypertension. Nitrendipine had opposite effects in comparison with vasodilators like hydralazine or minoxidil. Nitrendipine lowered heart weights, plasma atrial natriuretic peptide levels, and plasma renin activity, and was diuretic. Also, in spontaneously hypertensive rats that had been hypertensive for more than half of their life span prior to treatment, nitrendipine still had these effects. Nitrendipine prevented hypertension-induced mortality, even at subantihypertensive doses. Nitrendipine inhibited endothelin-1-induced DNA synthesis in isolated vascular smooth muscle cells as well as atherosclerotic plaque formation in cholesterol-fed rats.

Autoradiographic localization of [125I]-C-ANP compared to [125I]-ANP in rat tissue.

Whole-body autoradiography demonstrated the different distribution of [125I]-C-ANP and [125I]-ANP to rat tissues. Highest enrichment of radioactivity of both labelled peptides was found in the kidney. In some organs we found remarkable differences between [125I]-ANP and [125I]-C-ANP. In the kidney cortex, especially in the glomeruli, as well as in the endocardium, the zona glomerulosa and the medulla of the adrenal gland, where high levels of radioactivity after [125I]-ANP administration were detected, no or just few radioactivity was found after administration of [125I]-C-ANP. On the other hand in the kidney papilla and the outer subcortical medulla, characteristic blackening was found after [125I]-C-ANP administration. Those differences might be important for the understanding of pharmacological actions of ANP analogues.

Effects of different antihypertensive drug classes on survival in animal models.

Data on the influence of antihypertensive drug treatment on mortality of hypertensive rats are reviewed. Dihydropyridine calcium antagonists, verapamil, the angiotensin-converting enzyme (ACE) inhibitor captopril, and a triple combination of reserpine, hydralazine, and chlorothiazide normalized or markedly prolonged survival. Captopril was less effective in sodium chloride-induced, low-renin Dahl rat hypertension. Dihydralazine prolonged but did not nearly normalize survival. The K(+)-channel activator minoxidil was relatively ineffective. Data on diuretics or beta-blockers are insufficient or unavailable. Calcium antagonists nitrendipine and nimodipine and the ACE inhibitor captopril improved survival and prevented vascular lesions and calcinosis even at doses that failed to achieve normotension. All drugs that normalized survival also reduced heart weights. Minoxidil invariably increased heart weights and failed to improve survival. (Di)hydralazine assumed an intermediate position.

Influence of transplantation of parathyroid glands on blood pressure development in stroke prone spontaneously hypertensive rats and in normotensive Wistar Kyoto rats.

The influence of the parathyroid glands (PTG) on the development of high blood pressure (BP) in stroke prone spontaneously hypertensive (SHR/SP) and Wistar Kyoto (WKY) rats has been studied. After ablation of their own PTG's SHR/SP received PTG's from WKY rats and vice versa. After transplantation (TRPL) a normal calcium and parathyroid hormone (PTH) status was preserved during the whole observation period. One group of animals received a high salt diet (8% NaCl) for 4 weeks after transplantation, the other group received a normal rat chow for 3 months. In SHR/SP, which had PTG-transplants from WKY rats, the development of BP was clearly attenuated compared to sham operated rats in both experimental groups. WKY rats with PTG's from SHR/SP became hypertensive after two weeks during salt loading and after six weeks under normal diet. Sham operated WKY rats remained normotensive. The results demonstrate that the parathyroid gland is involved in the pathogenesis of hypertension, but the only known secretory product of PTG's parathyroid hormone, seems not to be responsible for these effects.

125I-endothelin-1 and 125I-big endothelin-1 in rat tissues: autoradiographic localization and receptor binding.

The potent vasoconstrictor peptide, endothelin-1 (ET-1), which exhibits a characteristically long-acting activity in vitro and in vivo, is thought to be generated in endothelial cells from a less active intermediate, big endothelin-1 (big ET-1). In addition to ET-1, big ET-1 is also present in the circulation. The autoradiographic localization of 125I-big ET-1 and 125I-ET-1 has been studied after intravenous administration in rat tissues. Highest enrichment of radioactivity was found in the kidney cortex for both peptides. Compared to blood levels, enrichment of radioactivity is also detected, in the vascular wall of the aorta. Comparing the radioactivity pattern of ET-1 and big ET-1, a nearly identical tissue distribution is observed, with the exception of the relative enrichment in the lung and the zona glomerulosa after administration of ET-1. Both radioligands show a specific and saturable binding to lung and kidney membranes. In the case of lung tissue, Ki values are 10(-10) M for endothelin-1 and 10(-8) M for big endothelin-1. This difference in affinities may account for the lack of binding of big endothelin-1 to lung tissue.

Therapy of diseased stroke-prone spontaneously hypertensive rats with nimodipine.

We investigated the therapeutic effect of nimodipine or parathyroidectomy in old, diseased stroke-prone spontaneously hypertensive rats by observing 98 male 1-year-old rats over 5 months. After stroke had occurred, the rats were divided into three groups: 1) parathyroidectomy, 2) nimodipine, and 3) controls. In the nimodipine group, the rats survived longer than those in the other groups. Blood pressure of the controls did not differ from the nimodipine-treated and parathyroidectomy animals. The increase in calcium content of brain and kidney tissues and of plasma renin activity, urea, and creatinine was attenuated by nimodipine or parathyroidectomy. The histology of the kidneys revealed widespread fibrinoid necrosis of arteries in all rats. In the nimodipine-treated or parathyroidectomy groups, healing of the lesions was detectable. Cerebral lesions were mainly characterized by fibrinoid necrosis. Nimodipine-treated as well as parathyroidectomied animals showed significantly fewer hypertensive cerebral lesions. In old, diseased stroke-prone spontaneously hypertensive rats, therapy with nimodipine or parathyroidectomy increased their survival rate. The cerebrovascular and renovascular lesions of treated animals were attenuated, and morphologic signs of healing were observed. Reduction of calcium overload by nimodipine or parathyroidectomy, even in an advanced stage of disease, had a therapeutic effect.

Development of hypertension in WKY rats after transplantation of parathyroid glands from SHR/SP.

We have investigated the role of the parathyroid gland (PTG) in the long-term development of blood pressure (BP) in stroke prone spontaneously hypertensive rats (SHR/SP) and Wistar Kyoto (WKY) rats. After ablation of their own PTGs, SHR/SP animals received PTGs from WKY rats and vice versa. Transplantation resulted in a normal calcium and parathyroid hormone status without signs of hypoparathyroidism. All animals received a high salt diet (8% NaCl) for 4 weeks after transplantation of PTGs. In SHR/SP, which received PTGs from WKY, development of high BP was clearly attenuated when compared to sham-operated SHR/SP rats. WKY rats with PTGs from SHR/SP rats became hypertensive, while WKY sham-operated animals remained normotensive. PTGs from SHR/SP rats are able to induce hypertension in normotensive WKY rats.

Influence of nifedipine on experimental arteriosclerosis.

The nonhemodynamic actions of nifedipine and some other calcium antagonists are reviewed with regard to their relevance to the vasculoprotective and antiarteriosclerotic action of calcium antagonists. Nifedipine, and in order of declining potency, verapamil and diltiazem were shown to inhibit vascular myocyte proliferation and migration. Also, the incorporation of cholesteryl esters into macrophages or myocytes was inhibited by dihydropyridines and verapamil but not by diltiazem. The cholesterol and calcium contents were found to be lowered in the aortae of hypercholesterinemic rabbits treated chronically with dihydropyridine calcium antagonists. Replacement of damaged vascular endothelium and internal elastic lamina was seen in hypertensive Dahl-S rats after 6 weeks of antihypertensive treatment with nifedipine. In addition to their blood-pressure lowering action, these nonhemodynamic effects might be involved in the prevention and reversal of hypertensive vascular disease and neuropathologic symptoms observed after the treatment of hypertensive rats with nifedipine or other dihydropyridine calcium antagonists, since these therapeutic effects were also seen after blood-pressure neutral doses.