Pathophysiology of the Belgrade rat

The Belgrade rat is an animal model of divalent metal transporter 1 (DMT1) deficiency. This strain originates from an X-irradiation experiment first reported in 1966. Since then, the Belgrade rat’s pathophysiology has helped to reveal the importance of iron balance and the role of DMT1. This review discusses our current understanding of iron transport homeostasis and summarizes molecular details of DMT1 function. We describe how studies of the Belgrade rat have revealed key roles for DMT1 in iron distribution to red blood cells as well as duodenal iron absorption. The Belgrade rat’s pathology has extended our knowledge of hepatic iron handling, pulmonary and olfactory iron transport as well as brain iron uptake and renal iron handling. For example, relationships between iron and manganese metabolism have been discerned since both are essential metals transported by DMT1. Pathophysiologic features of the Belgrade rat provide us with a unique and interesting animal model to understand iron homeostasis

Blood rheology adjustments in rats after a program of intermittent exposure to hypobaric hypoxia

Esteva, Santiago, Pere Panisello, Joan Ramon Torrella, Teresa Pagés, and Ginés Viscor. Blood rheology adjustments in rats after a program of intermittent exposure to hypobaric hypoxia. High Alt. Med. Biol. 10:275-281, 2009. Intermittent hypobaric hypoxia (IHH) exposure induces a rise in hemoglobin concentration and an increase in erythrocyte mass in both rats and humans. Although this response increases blood oxygen transport capacity, paradoxically, it could impair blood flow and gas exchange because of the blood viscosity alterations associated with the rising hematocrit. In the present study, male rats were subjected to an IHH program consisting of a daily 4-h session for 5 days/week until they had completed 22 days of hypoxia exposure in a hypobaric chamber at a simulated altitude of 5000 m. Blood samples were taken at the end of the exposure period (H) and at 20 (P20) and 40 (P40) days after the end of the program and were compared to control (C) maintained at sea- level pressure. Apparent blood viscosity (ηa) and plasma viscosity (ηp) were measured in a cone-plate microviscometer. Although the hematocrit significantly increased in the H group, blood apparent viscosity did not differ among groups, ranging from 7.67 to 6.57 mPa sec at a shear rate of 90 sec−1. Relative blood viscosity showed a clear increase (about 27%) in H rats, mainly due to the significant decrease in plasma viscosity. This finding could be interpreted as a compensatory response, which reduced the effect of increased erythrocyte mass volume on whole-blood viscosity. Oxygen delivery index and blood oxygen potential transport capacity remained unchanged in all groups. These data indicate that the IHH program has a deep but transitory effect on red cell parameters and a moderate effect on blood rheological behavior

Antihypertensive Action of Heparin: Role of the Renin‐Angiotensin Aldosterone System and Prostaglandins

Chronic subcutaneous administration of heparin consistently lowers blood pressure in hypertensive rats. This antihypertensive effect is related at least in part to a concomitant decrease in hematocrit. Groups of spontaneously hypertensive (SHR) and normotensive Wistar (NWR) rats were treated with subcutaneous heparin (700 U/d) for 6 weeks. Weekly determinations of systolic blood pressure (tail‐cuff) and hematocrit were done. Peripheral plasma renin activity, plasma aldosterone, plasma prostaglandins (PGs) (PGF2alpha, PGI2), thromboxane A2, and urinary kallikrein were measured. Blood pressure responses of acute and chronic heparin treatment to vasoconstrictor substances, including angiotensin I, angiotensin II, and norepinephrine, were determined. As before, heparin produced a significant (P < .01) decrease in hematocrit in both SHRs and NWRs, but a parallel decrease in blood pressure was noted only in SHRs. A significant (P < .001) increase in plasma renin activity was found in heparin‐treated SHRs and NWRs; however, a corresponding elevation of plasma aldosterone level was noted only in heparin‐treated NWR. Plasma aldosterone level significantly (P < .01) decreased in heparin‐treated SHRs. Plasma PGs and urinary kallikrein levels were not different among the groups. The blood pressure responses to vasoconstrictor substances were essentially similar among the heparin‐treated and control groups. These findings suggest that PGs or kallikrein have a slight or no role in determining the antihypertensive effect of heparin. Conversely, the results suggest that a reduced aldosterone level contributes to the antihypertensive mechanism of heparin