Systolic pressure predicts plasma vasopressin responses to hemorrhage and vena caval constriction in dogs

We have proposed that the reflex increase in arginine vasopressin (AVP) secretion in response to hypovolemia is due to arterial baroreceptor unloading. If arterial pressure is the key to the mechanism, the slope relating plasma AVP to arterial pressure should be the same in response to hemorrhage, a model of true hypovolemia, and in response to thoracic inferior vena caval constriction (IVCC), a model of central hypovolemia. We tested this hypothesis in conscious, chronically instrumented dogs (n = 8). The mean coefficient of determination (r(2)) values obtained from the individual regressions of log AVP onto systolic pressure (SP) and mean arterial pressure (MAP) in response to hemorrhage were 0.953 +/- 0.009 and 0.845 +/- 0.047, respectively. Paired comparisons indicated a significant difference between the means (P < 0.05), hence, SP was used in subsequent analyses. The mean slopes relating the log of plasma AVP to SP in response to hemorrhage and IVCC were -0.034 +/- 0.003 and -0.032 +/- 0.002, respectively, and the means were not significantly different (P = 0.7). The slopes were not altered when the experiments were repeated during acute blockade of cardiac receptors by intrapericardial procaine. Finally, sinoaortic denervation (n = 4) markedly reduced the slope in both the hemorrhage and IVCC treatments. We conclude that baroreceptors monitoring arterial pressure provide the principal reflex control of AVP secretion in response to hypovolemia.     

Effect of chronic and progressive aortic constriction on renal function and structure in rats

The purpose of this study was to evaluate the functional and structural renal damage observed in aortic-constricted hypertensive rats and to identify their possible relationship with transforming growth factor beta (TGF-beta) expression. Progressive renovascular hypertension was induced by progressive aortic constriction between the two renal arteries. Three months after constriction, the glomerular filtration rate (GFR), effective renal blood flow (ERBF), perfusion pressure (PP), urinary protein excretion (UPE) and urinary electrolyte excretion (U(Na)V and U(K)V) in the kidney above (right kidney, RK) and below the ligature (left kidney, LK) were measured. The cross-sectional corpuscular, capillary tuft and mesangial matrix area and tubulo-interstitial fibrosis were measured in tissue sections stained with Syrius Red using a computer-assisted image analysis system. TGF-beta was detected by immunohistochemistry. The functional parameters were similar in the two kidneys of aortic-constricted hypertensive rats (GFR-RK, 1.33+/-0.08 vs. LK, 1.18+/-0.08 mL/min; ERBF-RK, 9.23+/-1.32 vs. LK, 8.18+/-0.91 mL/min; RVR-RK, 28.3+/-3.9 vs. LK, 21.7+/-3.2 mmHg x min/mL). The RK was subject to a higher PP than the LK (176+/-7 vs. 128+/-5 mmHg, P < 0.05). UPE, U(Na)V, and U(K)V were greater in the RK than in the LK (UPE-RK, 512+/-61 vs. LK, 361+/-38 microg/30 min, P < 0.05; U(Na)V-RK, 0.056+/-0.012 vs. LK, 0.022+/-0.006 mEq/30 min, P < 0.05; UKV-RK, 0.042+/-0.006 vs. LK, 0.029+/-0.003 mEq/30 min, P < 0.05). Morphometric analysis revealed that the RK capillary tuft area and mesangial matrix area were higher than those in the LK. The LK had a higher degree of interstitial fibrosis than the RK. No significant differences in TGF-beta immunostaining were observed between the RK and the LK. In conclusion, the RK (subjected to hypertension) of aortic-constricted hypertensive animals developed glomerular fibrosis, only in the outer glomeruli whereas the LK developed mild interstitial fibrosis. Neither glomerular nor interstitial fibrosis seem to be responsible for the proteinuria observed in both kidneys.     

Pulmonary vascular responses to surgical chemodenervation and chemical sympathectomy in dogs

We investigated the effects of surgical peripheral chemoreceptor denervation, chemical sympathectomy with 6-hydroxydopamine (6-OHDA), and the peripheral chemoreceptor stimulant almitrine on multipoint pulmonary arterial pressure-cardiac index (PAP/Q) plots in 30 pentobarbital sodium-anesthetized dogs ventilated alternatively in hyperoxia [fraction of inspired O2, (FIO2) = 0.4] and hypoxia (FIO2 = 0.1). A hypoxic pulmonary vasoconstriction (HPV), i.e., a hypoxia-induced increase in PAP over the entire range of Q studied, from 2 to 5 l.min-1.m-2, was elicited in all the animals. Surgical denervation of the carotid and aortic chemoreceptors in a first group of nine dogs increased PAP at the lowest Q of 2 and 3 l.min-1.min-2 in hyperoxia and increased PAP at all levels of Q in hypoxia, so that HPV was enhanced. Chemical sympathectomy in a second group of eight dogs increased PAP at all levels of Q to a comparable extent in hyperoxia and hypoxia so that HPV remained unchanged. Almitrine (8 micrograms.kg-1.min-1 iv) in a third group of eight dogs increased PAP at all levels of Q in hyperoxia but had no effect on PAP/Q plots in hypoxia, so that HPV was inhibited. Almitrine had these same pulmonary vascular effects when administered to the chemodenervated and the sympathectomized dogs. Sham operation and a 2-h delay in a final group of five dogs had no effect on hyperoxic or hypoxic PAP/Q plots. We conclude that in intact dogs 1) the sympathetic nervous system reduces both hyperoxic and hypoxic pulmonary vascular tone, 2) stimulation of the peripheral chemoreceptors inhibits HPV, and 3) almitrine has direct pulmonary vasoconstricting effects in hyperoxia but not hypoxia.     

Effect of superior vena caval hypertension on alloxan-induced lung injury in dogs

To investigate how fast and to what extent superior vena caval hypertension (SVCH) increases lung water in acute increased-permeability state, we studied the time course of lung water accumulation for 3 h in anesthetized dogs under different treatments: 1) controls without intervention (5 dogs), 2) SVCH alone (5 dogs), 3) mild lung microvascular injury induced by low-dose alloxan (75 mg/kg) alone (5 dogs), and 4) SVCH coupled with low-dose alloxan (5 dogs). Neither low-dose alloxan alone nor SVCH alone [superior vena caval pressure (Psvc) = 11.0 +/- 3.1 (SD) mmHg] increased lung water significantly. The SVCH coupled with low-dose alloxan (Psvc = 11.3 +/- 2.7 mmHg) doubled extravascular lung thermal volume measured by the thermal-dye dilution technique within 1 h (5.3 +/- 0.9 ml/kg at base line and 10.9 +/- 4.7 ml/kg at 1 h), then remained unchanged (12.5 +/- 5.7 ml/kg at 3 h). This increase in lung water was confirmed by gravimetric method (5.69 +/- 1.71 g/g blood-free dry wt). We conclude that SVCH is one of the factors that may promote lung water accumulation in increased-permeability state.     

Effect of the blood lactate concentration on renal glutamine metabolism in dogs with chronic metabolic acidosis

It appears that glutamine and lactate are the principal substrates for the kidney in dogs with chronic metabolic acidosis. Accordingly, the purpose of this study was to determine if a higher or lower rate of renal lactate extraction would influence the rate of glutamine extraction at a constant rate of renal ATP turnover. The blood lactate concentration was 0.9 +/- 0.01 mM in 15 acidotic dogs. However, eight dogs with chronic metabolic acidosis had a spontaneous blood lactate concentration of 0.5 mM or lower. The kidneys of these dogs extracted considerably less lactate from the arterial blood (19 vs. 62 mumol/100 mL glomerular filtration rate (GFR]. Nevertheless, glutamine, alanine, citrate, and ammonium metabolism were not significantly different in these two groups of dogs. Renal ATP balance in acidotic dogs with a low blood lactate could only be achieved if a substrate other than additional glutamine were oxidized in that segment of the nephron which normally oxidized lactate; presumably a fat-derived substrate and (or) lactate derived from glucose was now the metabolic fuel at these more distal sites. When the blood lactate concentration was greater than 1.9 mM, lactate extraction rose to 219 mumol/100 mL GFR. Glutamine, alanine, citrate, and ammonium metabolism were again unchanged; in this case, ATP balance required substrate flux to products other than carbon dioxide, presumably, gluconeogenesis. It appears that renal ammoniagenesis is a proximal event and is independent of the rate of renal lactate extraction.     

Effect of chemical sympathectomy on the development of DOCA-salt hypertension in rats

Structurally based resistance and vascular reactivity of the posterior body to noradrenaline were studied in normotensive rats and rats with DOCA-salt hypertension. The hypertension was induced in rats with intact sympathetic nervous system and in rats subjected to neonatal sympathectomy with guanethidine. During the prehypertensive stage, vascular sensitivity of the smooth muscles to noradrenaline was enhanced, with structural lesions being observed only in steady hypertension. Elevation of arterial pressure was accompanied by an increased vascular response to the stimulation of the sympathetic nerves. Sympathectomy prevented arterial pressure elevation and structural alterations in the vessels.     

Decreased venous compliance in dogs with chronic renal hypertension.

Femoral vein (FV) pressure-volume relationships were measured in vitro in 14 dogs with chronic (more than 4 weeks), one-kidney perinephritic hypertension and in 13 unilaterally nephrectomized normotensive control dogs. Segments of FV were also examined histologically and analyzed for their water and electrolyte contents. Compared to controls: (I) the FV pressure-volume curves of hypertensive dogs were shifted toward the pressure axis (P is less than 0.05); (ii) calcaulated vagous compliance in the pressure range of 0-15 mm Hg was decreased (P is less than 0.05); and (iii) the water and sodium contents of vwins from hypertensive dogs were increased (P is less than 0.05). Histological examination of the FV from hypertensive and control dogs did not reveal significant differences. The findings indicate that the decreases in venous compliance that we have previously observed in the early stages (less than 4 weeks) of perinephritic hypertension in dogs persist into the chronic stage of hypertension. Venous wall "edema" may account for the decreased venous compliance in this form of hypertension.     

Effect of somatostatin on renal water handling in the dog

When somatostatin was infused into the left renal artery of anaesthetized, hydropenic dogs in doses ranging from 1 to 10 micrograms/min, it produced an increased flow of a more dilute urine from the ipsilateral kidney. Similar infusions in dogs undergoing a maximal water diuresis had no effect. If aqueous antidiuretic hormone (ADH) was administered intravenously into water-loaded dogs prior to the intraarterial infusion of somatostatin, this latter peptide was able to produce an augmented flow of a more dilute urine from the ipsilateral kidney. If the left kidney was made to excrete a concentrated urine in the face of maximal water loading by restricting arterial perfusion, then the infusion of somatostatin had no effect on urinary dilution, though this peptide could increase water excretion in hydropenic dogs when the left kidney was similarly restricted as to arterial inflow. In dogs undergoing a water diuresis that were given cyclic AMP (4 mg/min) into the left renal artery, a decrease in ipsilateral water excretion was observed. The subsequent infusion of somatostatin produced no urinary dilution. We conclude that somatostatin increases renal water excretion by antagonizing the ADH effect on the renal tubule, and that this event probably occurs at a pre-cAMP site within the cell.