1. Renal responses to changes in renal perfusion pressure were studied in anaesthetized hyperthyroid (thyroxine, 300 μg day −1 kg −1 ) and hypothyroid (methimazole, 0.03% via drinking water) rats to determine whether an abnormality in the pressure-diuresis-natriuresis phenomenon is involved in the resetting of kidney function in these disorders. 2. There were no significant differences between control and hypothyroid rats with respect to the relationships between renal perfusion pressure and absolute or fractional water and sodium excretion. However, in hyperthyroid rats the pressure-diuresis-natriuresis mechanism was impaired. 3. Renal blood flow and glomerular filtration rate were well autoregulated and there were no differences between control and hypothyroid rats at every level of renal perfusion pressure. A significantly lower glomerular filtration rate was observed in hyperthyroid rats when data were expressed per gram kidney weight, but glomerular filtration rate was similar to that of control rats when normalized by body weight. 4. The shift in the pressure-diuresis-natriuresis response of hyperthyroid rats is mainly due to an increase in tubular reabsorption. Blunting of the renal pressure-diuresis-natriuresis mechanism in hyperthyroid rats may represent the functional resetting of the kidney necessary for sustained hypertension. However, a normal pressure-natriuresis response was observed in hypothyroid rats, in which blood pressure was markedly reduced.
1. Evidence indicates that nitric oxide (NO) exerts a paracrine influence in the renal medulla. Increases in papillary blood flow are thought to be an important determinant of the renal response to extracellular volume expansion. Therefore, in the present study, we have evaluated the role of NO in mediating papillary blood flow (laser-Doppler flowmetry) and excretory responses to volume expansion with isotonic saline (3% body weight, 15 min). 2. Infusion of the NO synthesis inhibitor N ω -nitro-l-arginine methyl ester (10 μg min −1 kg −1 ), significantly attentuated the renal diuretic and natriuretic responses to volume expansion as well as the renal hydrostatic interstitial pressure increase induced by this manoeuvre. The percentages of the water and sodium excreted in 1 h by the N ω -nitro-l-arginine methyl ester-pretreated animals were 36% and 40% of the load, whereas those of the control animals were 44% and 65%, respectively. 3. In similar experiments performed in the exposed papilla of Munich Wistar rats, the same dose of N ω -nitro-l-arginine methyl ester reduced basal papillary blood flow and blunted the elevation in papillary blood flow induced by volume expansion (6% versus 16% in the control animals). 4. These results indicate that the inhibition of NO synthesis blunts the renal excretory and papillary responses to volume expansion, suggesting that NO modulates these responses through changes in papillary blood flow and renal interstitial hydrostatic pressure.
1. The purpose of the present investigation was to determine whether an abnormality of the renal papillary circulation is present in a well-established model of cirrhosis without ascites (carbon tetrachloride/phenobarbital). 2. Compared with the control animals, cirrhotic rats showed a reduced diuretic (61.0 ±5.1 versus 18.0 ±2.5%) and natriuretic (67.8 ±8.3 versus 29.6 ±3.6%) response to a volume expansion (3% body weight infusion of 0.9% NaCl). The volume expansion-induced increase in renal interstitial hydrostatic pressure was also blunted in the cirrhotic rats (control 9.3 ±0.9 versus cirrhotic 6.1±1.0 mmHg) and there were no differences in mean arterial blood pressure, renal blood flow or glomerular filtration rate between control and cirrhotic animals. 3. Papillary plasma flow was determined by the 125 I-albumin accumulation technique and expressed as mlmin −1 100 g −1 . In the basal state, papillary plasma flow was significantly lower in cirrhotic rats (59.1 ±4.4, n = 9) than in the control animals (81.8 ±6.9, n = 9). An isotonic saline expansion similar to the one described above significantly increased papillary plasma flow in control rats (108.4±9.1, n = 7) but did not change it in cirrhotic rats (60.2 ±4.9, n = 6). 4. Our results indicate the existence of a selective alteration in the renal papillary circulation in cirrhotic rats, both in the basal state and after a well-established vasodilatory stimulus. The reduced papillary plasma flow of the cirrhotic animals, probably mediated through changes in renal interstitial hydrostatic pressure, may participate in the sodium and water retention that precedes the development of ascites and may be an important mechanism mediating the blunted renal response to extracellular volume expansion.