Nitric oxide synthase blockade and body fluid volumes

Abstract

The influence of chronic nitric oxide synthase inhibition with N Gnitro-L-arginine methyl ester (L-NAME) on body fluid distribution was studied in male Wistar rats weighing 260-340 g. Extracellular, interstitial and intracellular spaces, as well as plasma volume were measured after a three-week treatment with L-NAME (»70 mg/kg per 24 h in drinking water). An increase in extracellular space (16.1 ± 1.1 vs 13.7 ± 0.6 ml/100 g in control group, N = 12, P<0.01), interstitial space (14.0 ± 0.9 vs 9.7 ± 0.6 ml/100 g in control group, P<0.001) and total water (68.7 ± 3.9 vs 59.0 ± 2.9 ml/100 g, P<0.001) was observed in the L-NAME group (N = 8). Plasma volume was lower in L-NAMEtreated rats (2.8 ± 0.2 ml/100 g) than in the control group (3.6 ± 0.1 ml/ 100 g, P<0.001). Blood volume was also lower in L-NAME-treated rats (5.2 ± 0.3 ml/100 g) than in the control group (7.2 ± 0.3 ml/100 g, P<0.001). The increase in total ratio of kidney wet weight to body weight in the L-NAME group (903 ± 31 vs 773 ± 45 mg/100 g in control group, P<0.01) but not in total kidney water suggests that this experimental hypertension occurs with an increase in renal mass. The fact that the heart weight to body weight ratio and the total heart water remained constant indicates that, despite the presence of high blood pressure, no modification in cardiac mass occurred. These data show that L-NAME-induced hypertension causes alterations in body fluid distribution and in renal mass. Key wordsNitric oxide (NO) has an important role in the physiologic control of blood pressure. Alterations in NO synthesis may be involved in the pathogenesis of hypertension. There is evidence that the short-term and long-term in vivo administration of nitric oxide synthase (NOS) inhibitors such as N G -nitro-L-arginine methyl ester (L-NAME) induces a doseand time-dependent increase in arterial blood pressure in conscious rats and adaptive changes in the functions of the kidney, heart and vessels (1). Three NOS isoforms (neuronal, inducible and endothelial) are expressed in the heart in a cell-specific manner (2) and in rat kidney, but it is unclear which NOS isoform(s) is/are responsible for the functional effects (3). The response to chronic NOS inhibition is likely to depend upon several factors, including the cellular source of NO, the amount released, the target tissue and interactions with neurohumoral factors (4). Recent investigations have shown that the chronic model of hypertension with L-NAME is generally associated with an archi-

Hemorheological Effects of Valsartan in L-NAME Induced Hypertension in Rats

“…4) are significantly increased in the hypertensive rats group (HTA) and significantly decreased after valsartan administration. Althought not determined by us, L-NAME induced hypertension doesn't induce significant changes in hematocrit values [21], meaning that the changes in blood viscosity aren't a result of hematocrit changes.…”

Developmental Effects of 7 Hz, Square Wave Magnetic Fields and Nitric Oxide Modulation on Organ Systems

“…The only notable effect of perinatal NO modulation was the ability of NMA to decrease kidney weight. Interestingly, this trend is the reverse of what has been found to occur with chronic NO inhibition administered in adulthood [35]. The time at which NO modulation occurs might therefore determine the vector of effect on kidney mass.…”