Lateral cephalometric standards of Germans with normal occlusion from 6 to 17 years of age.

The aim of this study was to analyze sagittal and vertical dentofacial dimensions in subjects with normal occlusions during the juvenile and adolescents age periods to establish age- and gender-specific lateral cephalometric standard values for Germans during their active growth period. The study group consisted of a sample of 32 untreated subjects with normal occlusions. Lateral cephalograms were analyzed at 11 consecutive stages, from 6-13 and from 15-17 years of age. A customized cephalometric analysis was used to measure 53 variables. Statistical comparisons of gender-specific differences were performed by means of Mann-Whitney U tests.Anterior and posterior cranial base lengths, midfacial length as well as mandibular length were recorded to be significantly larger in male subjects at the age of 6 years. For most of the linear measurements, significantly larger craniofacial distances were recorded in males from the age of 15 years onward. There were no statistically significant gender differences with regard to most angular measurements at subsequent age groups. Soft tissue analysis revealed flatter profiles in females than in males from the age of 10-11 years onward, while age-dependent changes in the soft tissue profile were similar in both genders.In untreated subjects with normal occlusion craniofacial development of the hard and soft tissues can be considered age- and gender-dependent. Therefore age- and gender-specific differences of linear craniofacial distances should be taken into account for diagnosis and treatment planning in children and adolescents. The present results can be used as reference values for children and adolescents of German origin.

Evidence for a preglomerular oxygen diffusion shunt in rat renal cortex.

Although blood flow to the renal cortex is high and oxygen extraction is low, the renal cortex is remarkably susceptible to hypoxia. Because erythropoietin production has been localized mainly to the renal cortex, the aim of this study was to find a common denominator for both the high susceptibility to hypoxia and oxygen sensing within the renal cortex. By direct measurement of oxygen pressure with microcoaxial needle sensors at superficial glomeruli of the in situ kidney of anesthetized Munich-Wistar-Frömter rats, we obtained mean partial pressure of O2 (PO2) values of 46 +/- 13 (SD) mmHg (n = 71). The simultaneously measured systemic PO2 in arterial blood was 90 +/- 8 mmHg (n = 54). Changing the respirator gas from air to pure oxygen enhanced systemic arterial PO2 to 593 +/- 27 mmHg, whereas PO2 at the superficial glomeruli increased only to a mean of 80 +/- 28 mmHg (n = 71). These data suggest significant preglomerular shunting of oxygen within the cortical vasculature, most likely between interlobular vessels, which are arranged in a countercurrent fashion and represent quantitatively the largest contact area between arteries and veins within the renal cortex.

Sodium reabsorption in the isolated perfused kidney of normotensive and spontaneously hypertensive rats.

Kidneys of 3-month-old spontaneously hypertensive rats (SHR) of the Münster strain and age- and weight-matched normotensive rats (Wistar-Kyoto; WKY) were isolated and perfused at a constant pressure of 100 mmHg with a modified, albumin-free Krebs-Henseleit solution. Fractional Na+ reabsorption, which is independent of the glomerular filtration rate under these conditions, was significantly elevated in SHR kidneys compared with WKY kidneys during 90 min of perfusion (P less than 0.01). Renal perfusion flow rates did not differ between SHR and WKY. These data support the concept of an intrinsic renal abnormality in Na+ excretion that may contribute to the maintenance of hypertension in SHR.

Renal mesangium is a target for calcitonin gene-related peptide.

Rat calcitonin gene-related peptide (CGRP alpha; EC50, 1 nM) was shown to stimulate cAMP formation in cultured rat renal mesangial cells. CGRP concentration dependently (EC50, 1 nM) also inhibited contraction of mesangial cells by angiotensin II (10 nM). Angiotensin II (10 nM) caused a transient increase of the intracellular calcium concentration from 140 nM to 480 nM in the mesangial cells, but these calcium transients were not altered by CGRP. CGRP (10 nM) decreased vascular resistance in the isolated rat kidney perfused at constant pressure (100 mm Hg; P less than 0.01). The decreased vascular resistance was accompanied by a rise of the glomerular filtration fraction. CGRP, moreover, attenuated the effects of angiotensin II on renal vascular resistance and glomerular filtration (P less than 0.01). In conclusion, CGRP causes relaxation of renal mesangial cells and decreases renal vascular resistance. As a result CGRP raises glomerular filtration and the filtration fraction. The effect may be linked to cyclic AMP formation. Thus, regulation of renal vascular and glomerular function may represent a novel action of CGRP apart from its cardiovascular effects.

Transmission of hypertension in rats by cross circulation.

Cross circulation was performed in 54 couples of spontaneously hypertensive and normotensive rats. Blood was pumped through two anastomoses between the carotid arteries and external jugular veins in both directions with equal flow rate. In normotensive rats cross-circulated with untreated spontaneously hypertensive rats mean arterial pressure increased by 20.9 +/- 12.2 mm Hg (p less than 0.01). Administration of digoxin antibody in a dose binding 0.25 mg digoxin to the spontaneously hypertensive rats before cross circulation prevented the transmission of hypertension to the normotensive rat, whereas chemical sympathectomy with 6-hydroxydopamine and intravenous injection of inactive Fab fragments had no inhibitory effect. It is concluded that, in this strain of spontaneously hypertensive rats, a circulating hypertensive factor exists. The factor binds to digoxin antibody and is not produced in sympathetic nervous tissue.

Effect on blood pressure of chemically induced renomedullectomy in normotensive and spontaneously hypertensive rats.

An antihypertensive function in systemic blood pressure control has been attributed to the renal medulla. In order to examine this hypothesis normotensive and spontaneously hypertensive rats of the Münster strain (SHR) were chemically renomedullectomized by 2-bromoethylamine hydrobromide (BEA), injected intraperitoneally in a single dose of 200 mg/kg body weight. Within 5 weeks blood pressure of the BEA-treated normotensive rats and SHR rose by 17.2 +/- 15.2 and 27.7 +/- 21.0 mmHg (mean values +/- s.d; P less than 0.01), respectively, returning to baseline after 2 further weeks. Blood pressure was unchanged in the normotensive rats and SHR controls that were given isotonic saline instead of BEA solution. During maximum blood pressure in BEA-treated animals histological signs of severe renomedullary inflammation with papillary necrosis were demonstrable, while urine flow rates were elevated. Despite these disturbances renal function remained normal. These similar responses make it unlikely that a lack of a renomedullary vasodilator plays a major role in the pathogenesis of spontaneous hypertension in the Münster strain.

A circulating hypertensive factor in primary hypertension: effect of antihypertensive therapy.

In this study the role of a humoral hypertensive factor in spontaneously hypertensive rats (SHR) of the Münster strain was examined by cross-circulation. It was demonstrated that hypertension of the SHR could be transmitted to cross-circulation normotensive Wistar-Kyoto rats. The results led to the following conclusion: primary hypertension is caused by a circulating factor which is produced by kidneys and adrenals and suppressed by acute volume depletion and chronic dietary salt restriction. The antihypertensive effect of nifedipine probably leads to a compensatory stimulation of the hypertensive factor in SHR.

The effect of antihypertensive treatment on the circulating hypertensive factor in the spontaneously hypertensive rat.

To elucidate the role of circulating hypertensive factors in the spontaneously hypertensive rat and the effects of antihypertensive treatment on the circulating hypertensive factor, cross circulation was performed in 54 couples of spontaneously hypertensive and normotensive rats. In normotensive rats cross-circulated with untreated spontaneously hypertensive rats mean arterial pressure increased by 20.9 +/- 12.2 mm Hg (p less than 0.01). Increases in mean arterial pressure were also obtained by cross-circulation with spontaneously hypertensive rats pretreated with propranolol, furosemide, and nifedipine. Mean arterial pressure was not changed by cross circulation after pretreatment of the spontaneously hypertensive rats with alpha methyldopa. It is concluded that in this strain of spontaneously hypertensive rats a circulating hypertensive factor exists, the secretion of which can be suppressed by the centrally acting drug, alpha methyldopa. Therefore either the central nervous system may take part in the regulation of the factor or the factor may be synthetized in the central nervous system.

Arterial resistance vessels in primary hypertension--evidence for altered cellular Ca2+ metabolism.

The role of intracellular free Ca2+ in arterial smooth muscle was investigated in aortic smooth muscle cells from spontaneously hypertensive and normotensive rats, as well as in porcine aortic smooth muscle. Intracellular free Ca2+ in aortic smooth muscle from spontaneously hypertensive rats was elevated. Incubation of porcine aortic smooth muscle with plasma from essential hypertensive and normotensive subjects revealed a humoral factor in subjects with essential hypertension, which increased intracellular free Ca2+. Cross-circulation experiments between spontaneously hypertensive and normotensive rats demonstrated a transmission of hypertension to the normotensive animals as a result of a circulating hypertensive factor possibly produced in the kidneys and adrenals. The experiments suggest that vasoconstriction in primary hypertension may be caused by a humoral factor that increases intracellular free Ca2+ in arterial smooth muscle.

Effects on blood pressure of cross circulation between spontaneously hypertensive and normotensive rats.

In order to examine the role of humoral factors for the development of hypertension in the spontaneously hypertensive rat of the Münster strain (SHR) cross circulation experiments with normotensive Wistar Kyoto rats were performed. Cross circulation between SHR and normotensive rats for 30 min increased mean arterial pressure in the latter by 29.1 +/- 7.6 mm Hg (p less than 0.01). Transmission of hypertension by cross circulation was abolished by nephrectomy, adrenalectomy, volume depletion or chronic salt restriction in the SHR. It is concluded that hypertension in SHR is caused by a circulating hypertensive agent produced in kidneys and adrenals, the secretion of which can be suppressed by volume or salt depletion.

Humoral factors in primary hypertension.

In 56 spontaneously hypertensive rats of the Muenster strain, either parabiosis or cross circulation was performed with normotensive Wistar Kyoto rats. Crossed circulation was made through the common carotid arteries and external jugular veins using a peristaltic pump. In parabiosis and in cross-circulation experiments, hypertension was transmitted from spontaneously hypertensive to normotensive rats. Nephrectomy or adrenalectomy in the spontaneously hypertensive rat before cross circulation abolished this effect. After volume depletion in the hypertensive animals, hypertension was not transmitted either. Furthermore, the effect of plasma fractions from essential hypertensives (n = 20) on blood pressure of normotensive rats was studied. Substances with molecular weights higher than 6000-8000 and lower than 500 were removed from 60-ml plasma by ultrafiltration and dialysis. After chromatography on a Bio-Gel P-4 or P-2 column, three to four fractions were formed according to the results of UV spectrophotometry and concentrated to 0.5 ml. One fraction from hypertensive plasma containing substances with molecular weights between 1000 and 2000 increased blood pressure in the rat by 16.3 +/- 8.2 mmHg within 10 minutes when injected intravenously. The respective fractions from normotensive rat plasma increased blood pressure by 3.6 +/- 2.1 mmHg (p less than 0.01). The results demonstrate a circulating hypertensive factor both in spontaneously hypertensive rats and in essential hypertensives, which may be crucial for the pathogenesis of essential hypertension.

Humoral factors in the pathogenesis of primary hypertension.

In 42 spontaneously hypertensive rats of the Münster strain either parabiosis or cross circulation with normotensive Wistar Kyoto rats was performed. Cross circulation was made through the common carotid arteries and external jugular veins using a peristaltic pump. In parabiosis and in cross circulation experiments hypertension was transmitted from the spontaneously hypertensive rats to normotensive rats. Nephrectomy or adrenalectomy in the spontaneously hypertensive rat before cross circulation abolished this effect. After volume depletion in the hypertensive animals hypertension was not transmitted either. It is concluded that humoral factors causing vasoconstriction play an essential role in the development of hypertension in the spontaneously hypertensive rat.