No abstract

The reversibility of functional and structural microvascular alterations in chronic renal hypertension has not been established. Twelve weeks after surgery to induce hypertension, in vivo arteriolar and venular dimensions were measured in the cremaster muscle of rats with one-kidney, one-clip hypertension (1K1C), rats in which the clip was removed after 8 weeks (1KNT), and controls. Systolic blood pressure was significantly elevated after 3 days in 1K1C rats and reached a plateau by 6 weeks. In 1KNT rats, systolic blood pressures were similar to 1K1C rats but were normalized 1 day after unclipping. A marked medial-intimal hypertrophy was found by histological techniques in the thoracic and abdominal aortae (45% and 69%, respectively) but not in cremaster feeding arteries of 1K1C rats. These arterial changes were reversed after unclipping. In 1K1C rats, medial-intimal area decreased in first- through fourth-order (1A, 2A, 3A, and 4A) arterioles along with a decline in relaxed diameter (41%, 30%, 20%, and 21%, respectively), which was only partially restored after unclipping. Heart weight was increased by 67% in 1K1C rats, but it did not differ between 1KNT and controls. Therefore, the reversal of chronic renal hypertension can normalize gross structural alterations in the heart and large vessels, but more time may be required to normalize completely the arteriolar changes. These data indicate that long-term structural adaptations in renal hypertension are different in arterioles and arteries, and they may be related to chronic changes in blood flow and/or pressure.

Arteriolar vasoconstriction, structural reductions in dilated diameter, and rarefaction have been observed in vascular beds with chronic renal hypertension. To determine their pressure or flow dependence, these functional and structural parameters were studied in the developing and chronic stages of coarctation hypertension in the cremaster muscle, a normotensive skeletal muscle bed that is protected from the effects of elevated microvascular pressures. Hypertension was produced in rats by placing a silver clip around the abdominal aorta above the branches of the renal arteries. In hypertensive rats, resting diameters were reduced in second-order arterioles after 4 and 8 wk, in third-order arterioles after 2, 4, and 8 wk, and in fourth-order arterioles after 4 and 8 wk, vs. controls. Vascular tone was elevated in second-order arterioles after 2, 4, and 8 wk and in third- and fourth-order arterioles after 8 wk in hypertensive rats. No increases in medial-intimal area were found at any stage of hypertension in any arteriolar order. The density of small arterioles (3rd-5th orders) was reduced by 20% in hypertensive rats at 8 wk but was unchanged at the other time periods. These arteriolar alterations, especially the absence of structural reductions in diameter, are attenuated compared with those observed in one-kidney, one-clip hypertension and suggest that most of the arteriolar alterations that occur in renal hypertension are pressure or flow dependent.

Arteriolar internal and external diameters in the cremaster muscle of two-kidney, one clip hypertensive rats (2K1C) were measured in vivo with video microscopy, both before and after the topical application of adenosine (10~4 M). Arteriolar density was determined by stereologic techniques. Mean arterial blood pressure was significantly elevated in the 2K1C rats, rising to 186±6 mm Hg by 8 weeks compared with 113±4 mm Hg in controls. Lumens of larger arterioles showed a structural reduction at 2 weeks of hypertension and remained at the same level through 8 weeks, while arterioles of control rats showed a progressive increase in diameter with age (101±6 /tin in 2K1C vs. 158±8 /im in controls at 8 weeks after operation). Wall-to-lumen ratios of larger arterioles were significantly increased at 2, 4, and 8 weeks of hypertension, but cross-sectional wall area was significantly reduced at 8 weeks. In two-kidney, one clip hypertensive rats (2K1C), the renin-angiotensin system plays an essential role in developing and maintaining hypertension.7 Increased activity of the sympathetic nervous system and vascular action of vasopressin are also involved.8 -10 Therefore, strong vasoconstriction is anticipated in this model of hypertension.11 In the initial stage of 2K1C hypertension, Meininger et al 12 found small arteriolar tone in the cremaster muscle to be increased, whereas larger arteriolar diameters were unchanged or even enlarged. After 4 weeks of hypertension, larger arteriolar diameters were significantly reduced but small arteriolar diameters were not different Received August 16, 1988; accepted February 6, 1989. from those of control rats. 13 However, these studies did not clarify whether the reduced lumen sizes in the larger arterioles were structural or functional. The purpose of the present study was to investigate the functional and structural changes of all four orders of arterioles of the cremaster muscle, from 2 to 8 weeks of 2K1C hypertension, and to determine if any structural reductions in lumen size are related to vascular wall hypertrophy. Materials and Methods Production of HypertensionMale Wistar rats (Charles River Laboratory, Inc, Wilmington, Massachusetts) were anesthetized with ketamine hydrochloride (60 mg/kg i.p.) and xylazine (10 mg/kg i.p.) at the age of 6-7 weeks. Body weight was 177±3 g in the control group and 177±4 g in the hypertensive group. Through a midline laparotomy, a silver clip with a gap of 0.20 mm was placed on the left renal artery. Control rats were treated in the same manner as the hypertensive rats, except no clip was applied. Penicillin G (25,000 units i.m.) was injected after the surgery. The rats were individually caged, fed Purina rat chow and water ad libitum, and maintained on a 12-hour light/

It has been demonstrated that bolus injections of a vasoconstrictor derived from endothelial cells, endothelin 1 (ET-1), constricts isolated arteries and increases blood pressure in animals when infused intravenously. The purpose of this study was to examine the direct effects of intrarenal infusions of ET-1 on renal function at doses that do not alter systemic arterial pressure. The effects of ET-1 on renal hemodynamics and electrolyte excretion were examined during 40 min of intrarenal infusions of ET-1 at rates of 1.15 and 5 ng.kg-1.min-1. Infusion of ET-1 (1.15 ng.kg-1.min-1) resulted in a transient increase in renal blood flow (RBF) followed by a progressive vasoconstriction, which reduced RBF by 23%. ET-1 decreased glomerular filtration rate (GFR) and had no significant effect on filtration fraction. Intrarenal infusion of ET-1 (1.15 ng.kg-1.min-1) had no effect on fractional excretion of sodium (FENa) or potassium. Infusion of ET-1 at a higher dose (5 ng.kg-1.min-1) produced further reductions in RBF, GFR, and FENa. These data indicate that ET-1 is a potent renal vasoconstrictor that could play a role in controlling renal hemodynamics.

Four commercial assay kits to measure serum ferritin were compared to establish the degree of agreement and interchangeability between the different techniques based on the intraclass correlation coefficient (ri). Radioimmunoassay, microparticle enzyme immunoassay, enzyme-linked immunosorbent assay, and chemiluminescent immunoassay systems were used. The Pearson product-moment correlation factor (r) between any two methods was at least 0.98, and the intercept of the regression equations ranged from -0.613 to 3.797, indicating that the methods were comparable. Furthermore, the intraclass correlation coefficient (ri) was at least 0.98, suggesting that the methods were interchangeable.

The anaemia of prematurity has been attributed to an insufficient erythropoietin (Epo) level. However, haemopoiesis is known to be regulated by a cohort of growth factors including interleukin-3 (IL-3), IL-6, stem cell factor (SCF), granulocyte monocyte-colony stimulating factor (GM-CSF) and insulin-like growth factors-I and -II (IGF-1, IGF-II). Circulating levels of these growth factors were measured in cord blood at the following gestational ages: 25-28 weeks, 29-32 weeks, 33-36 weeks and > 37 weeks. This study indicates that low concentrations of IGFs as well as a low Epo level in early gestational ages may play a role in anaemia of prematurity.

Paediatric subjects are able to donate the required units of blood as they have a good Epo response to mild anaemia. The amount of blood donated did not exceed their total mobilisable iron and the iron supplement was adequate for red cell synthesis.