Effect of vagotomy and thoracic sympathectomy on responses of the monkey to water immersion

Cardiopulmonary stretch receptors have been implicated as part of a reflex mechanism linking changes in blood volume to changes in renal excretion. Experiments were performed to determine whether total denervation of these receptors by combined cervical vagotomy and thoracic sympathectomy affects the renal responses of the monkey to head-out water immersion, a maneuver that translocates blood to the thorax and elicits an increase in renal salt and water excretion. Macaca fascicularis monkeys first underwent chronic bilateral thoracic sympathectomy or sham denervation performed in two stages a week apart. One to two weeks later, they were anesthetized with pentobarbital sodium, and the sympathectomized animals underwent bilateral cervical vagotomy. Control renal function did not differ between the two groups. Immersion of 90-min duration increased central venous and mean arterial pressures by similar amounts in both groups, but heart rate increased only in the sham-denervated animals. Denervation did not affect the magnitudes or delay the times of onset of the increases in urine flow, absolute and fractional sodium excretion, and osmolar and free water clearances occurring with immersion. These results demonstrate that in the anesthetized monkey cardiopulmonary receptors are not necessary for eliciting the renal responses to immersion.     

Sympathetic-renal interaction in chronic arterial pressure control

The effects of neonatal sympathectomy of donors or recipients on posttransplantation arterial pressure were investigated in spontaneously hypertensive rats (SHR) by renal transplantation experiments. Conscious mean arterial pressure (MAP) and renal vascular resistance were 136 +/- 1 mmHg and 15.5 +/- 1.2 mmHg x ml(-1) x min x g in sympathectomized SHR (n = 8) vs. 158 +/- 4 mmHg (P < 0.001) and 20.8 +/- 1.1 mmHg x ml(-1) x min x g (P < 0.05) in controls (n = 10). Seven weeks after transplantation of a kidney from neonatally sympathectomized SHR donors, MAP in SHR recipients (n = 10) was 20 mmHg lower than in controls transplanted with a kidney from hydralazine-treated SHR (n = 10) (P < 0.05) associated with reduced sodium sensitivity of MAP. Neonatal sympathectomy also lowered MAP in F1-hybrids (F1H; SHR x Wistar-Kyoto rats). Within 6 wk after transplantation, renal grafts from untreated SHR increased MAP by 20 mmHg in sympathectomized F1H (n = 10) and by 35 mmHg in sham-treated F1H (n = 8) (P < 0.05). Neonatal sympathectomy induces chronic changes in SHR kidney function leading to a MAP reduction even when extrarenal sympathetic tone is restored. Generalized reduction in sympathetic tone resets the kidney-fluid system to reduced MAP and blunts the extent of arterial pressure rise induced by an SHR kidney graft.     

Cerebral intraventricular 6-hydroxydopamine prevents vascular changes in the mineralocorticoid hypertensive rat

The effect of cerebral intraventricular administration of 6-hydroxydopamine (6-OHDA) on blood pressure and vascular smooth muscle responsiveness in deoxycorticosterone acetate (DOCA)-treated rats was assessed. Rats treated with 6-OHDA and DOCA had significantly lower systolic blood pressures (142 +/- 8 mm Hg) than rats treated with DOCA alone (185 +/- 5 mm Hg). After 5 weeks of DOCA treatment, femoral arteries and aortae were excised from these rats, cut helically into strips, and placed in a muscle bath to record isometric force. Dose-response curves to serotonin were shifted to the left in femoral arteries from DOCA-treated rats compared to both control and 6-OHDA-DOCA-treated rats (ED50: DOCA = 6.8 X 10(-8) M, control = 27.9 X 10(-8) M, 6-OHDA-DOCA = 13.4 X 10(-8) M). Arachidonic acid, the prostaglandin precursor, produced greater maximal contractions in femoral artery strips of DOCA-treated rats (358 +/- 56 mg) than in those from controls (115 +/- 31 mg). The maximal response to arachidonic acid in arteries from 6-OHDA-DOCA rats (203 +/- 78 mg) was not different from control values. Ouabain produced a greater maximal response in aortic strips from DOCA rats (658 +/- 165 mg) compared to those from control (196 +/- 72 mg) or 6-OHDA-DOCA (309 +/- 87 mg) rats. We conclude that increased vascular responsiveness to serotonin, arachidonic acid, and ouabain in DOCA hypertensive rats is secondary to a central action of the mineralocorticoid.     

Neonatal sympathectomy reduces NADPH oxidase activity and vascular resistance in spontaneously hypertensive rat kidneys

Neonatal sympathectomy reduces arterial pressure in spontaneously hypertensive rats (SHR). In SHR transplanted with a kidney from sympathectomized SHR, arterial pressure was lower and less Na+ sensitive than in SHR transplanted with a kidney from hydralazine-treated SHR. This study was performed to identify underlying renal mechanisms. Tests for differential renal mRNA expression of nine a priori selected genes revealed robust differences for renal medullary expression of the NADPH oxidase subunit p47phox. Therefore, we investigated the effects of neonatal sympathectomy on renal mRNA expression of NADPH oxidase subunits, NADPH oxidase activity, and renal function. In 10-wk-old sympathectomized SHR fed a 0.6% NaCl diet, medullary p47phox and gp91phox expression was 40% less than in hydralazine-treated SHR. Also, after a 1.8% NaCl diet, medullary p47phox mRNA expression was lower in sympathectomized than in hydralazine-treated SHR. We found lower cortical (-30%, P<0.01) and medullary (-30%, P<0.05) NADPH oxidase activities in sympathectomized than in hydralazine-treated or untreated SHR. Glomerular filtration rate, renal blood flow, medullary blood flow, and fractional Na+ excretion in kidney grafts from sympathectomized and hydralazine-treated donors (n=8 per group) were similar at baseline and in response to a 20-mmHg rise in renal perfusion pressure. Renal vascular resistance was lower in kidneys from sympathectomized than hydralazine-treated donors (25+/-2 vs. 32+/-4 mmHg.min.ml-1, P<0.05). The results indicate that the sympathetic nervous system contributes to the level of renal NADPH oxidase activity and to perinatal programming of alterations in renal vascular function that lead to elevated renal vascular resistance in SHR.     

Effect of chronic treatment with deoxycorticosterone acetate on content of a natriuretic substance in atria of rats

Chronic (72 days) administration of deoxycorticosterone acetate (DOCA), with or without saline as the sole drinking fluid, depleted atria of rats of their diuretic and natriuretic activities. Chronic ingestion of saline as the sole drinking fluid did not affect the diuretic, natriuretic, and kaliuretic activities of atria compared with those of rats receiving water to drink. Since systolic blood pressure of the DOCA-treated group did not differ significantly from that of the untreated control group, the decrease in potency of atrial extract from DOCA-treated rats most likely occurred in response to increases in extracellular and vascular volumes. The ability of DOCA to decrease diuretic and natriuretic activities of atria was dose dependent. The decreased activities of the atria of DOCA-treated rats could reflect an increased production and turnover of atrial natriuretic factor. Additional studies revealed an increased diuretic and natriuretic responsiveness of DOCA-treated recipients to atrial extract from untreated rats. Thus, the results of these studies suggest that chronic treatment with DOCA reduced the natriuretic and diuretic potencies of atrial extract and increased renal responsiveness to it.     

Effects of chronic sympathectomy on locally mediated cutaneous vasodilation in humans.

In human skin, the vasodilator response to local heating includes a sensory nerve-dependent peak followed by a nadir and then a slower, nitric oxide-mediated, endothelium-dependent vasodilation. To investigate whether chronic sympathectomy diminishes this endothelium-dependent vasodilation, we studied individuals who had previously undergone surgical T(2) sympathectomy (n = 9) and a group of healthy controls (n = 8). We assessed the cutaneous vascular response (laser-Doppler) to 30 min of local warming to 42.5 degrees C on the ventral forearm (no sympathetic innervation) and the lower legs (sympathetic nerves intact). Lower body negative pressure (LBNP) was measured to confirm sympathetic denervation. During local warming in sympathectomized individuals, vascular conductance reached an initial peak at both sites [achieving 1.73 +/- 0.22 laser-Doppler units (LDU)/mmHg in the forearm and 1.92 +/- 0.21 LDU/mmHg in the leg]. It then decreased to a nadir in the innervated leg [to 1.77 +/- 0.23 LDU/mmHg (P < 0.05)] but not in the sympathectomized arm (1.69 +/- 0.21 LDU/mmHg; P > 0.10). The maximal vasodilation seen during the slower phase was not different between limbs or between groups. Furthermore, LBNP caused a 44% reduction in forearm vascular conductance (FVC) in control subjects, but FVC did not decrease significantly in sympathectomized individuals, confirming sympathetic denervation. These data indicate that endothelial function in human skin is largely preserved after sympathectomy. The altered pattern of the response suggests that the nitric oxide-dependent portion may be accelerated in sympathectomized limbs.     

Chronic angiotensin II infusion attenuates the renal sympathoinhibitory response to acute volume expansion

In this study the hypothesis was tested that chronic infusion of ANG II attenuates acute volume expansion (VE)-induced inhibition of renal sympathetic nerve activity (SNA). Rats received intravenous infusion of either vehicle or ANG II (12 ng. kg(-1). min(-1)) for 7 days. ANG II-infused animals displayed an increased contribution of SNA to the maintenance of mean arterial pressure (MAP) as indicated by ganglionic blockade, which produced a significantly (P < 0.01) greater decrease in MAP (75 +/- 3 mmHg) than was observed in vehicle-infused (47 +/- 8 mmHg) controls. Rats were then anesthetized, and changes in MAP, mean right atrial pressure (MRAP), heart rate (HR), and renal SNA were recorded in response to right atrial infusion of isotonic saline (20% estimated blood volume in 5 min). Baseline MAP, HR, and hematocrit were not different between groups. Likewise, MAP was unchanged by acute VE in vehicle-infused animals, whereas VE induced a significant bradycardia (P < 0.05) and increase in MRAP (P < 0.05). MAP, MRAP, and HR responses to VE were not statistically different between animals infused with vehicle vs. ANG II. In contrast, VE significantly (P < 0.001) reduced renal SNA by 33.5 +/- 8% in vehicle-infused animals but was without effect on renal SNA in those infused chronically with ANG II. Acutely administered losartan (3 mg/kg iv) restored VE-induced inhibition of renal SNA (P < 0.001) in rats chronically infused with ANG II. In contrast, this treatment had no effect in the vehicle-infused group. Therefore, it appears that chronic infusion of ANG II can attenuate VE-induced renal sympathoinhibition through a mechanism requiring AT(1) receptor activation. The attenuated sympathoinhibitory response to VE in ANG II-infused animals remained after arterial barodenervation and systemic vasopressin V(1) receptor antagonism and appeared to depend on ANG II being chronically increased because ANG II given acutely had no effect on VE-induced renal sympathoinhibition.     

Chemical sympathectomy decreases alveolar hypoxic vasoconstriction in lambs but not in sheep

We studied the role of the sympathetic nervous system in the augmented vasoconstrictor response of the newborn lamb, compared with the adult sheep, by producing a chemical sympathectomy with 6-hydroxydopamine (6-OHDA). Seven lambs, age 4-16 days, and five sheep, age 2 yr, were anesthetized and intubated with a double-lumen endotracheal tube, allowing ventilation of one lung with O2 to maintain systemic oxygenation while the contralateral lung was ventilated with N2 as a hypoxic challenge. Distribution of perfusion to each lung was evaluated using positron scintigraphy after inferior vena caval injections of 13N, a positron-emitting isotope. In the lambs, prior to 6-OHDA, distribution of perfusion to the test lung was 43 +/- 3% of total lung perfusion during bilateral O2 ventilation and fell with hypoxia to 24 +/- 2%, a reduction of 44 +/- 3% during N2 ventilation as compared with O2 ventilation. After 6-OHDA, hypoxic challenge reduced perfusion by only 22 +/- 2% (P less than 0.01 compared with pre-6-OHDA). In the adult sheep, hypoxic vasoconstriction reduced perfusion to the test lung by 28 +/- 2% but was unaffected by 6-OHDA. Absence of rise in pulmonary vascular resistance (PVR) or femoral artery pressure (Pfa) in response to Tyramine infusions after 6-OHDA confirmed complete sympathectomy in lambs and sheep. Persistent increases in PVR and Pfa to infusions of prostaglandin F2 alpha before and after 6-OHDA showed that the loss of alveolar hypoxic vasoconstriction in the lamb was specific. Thus sympathetic innervation may contribute to the greater strength of alveolar hypoxic vasoconstriction found in lambs than in sheep.     

Molecular advantage of diferric transferrin in delivering iron to reticulocytes: a comparative study

Administration of aprotinin, a kallikrein inhibitor, to anesthetized rats infused with 0.9% saline solution to expand the extracellular fluid volume resulted in blunted natriuresis and diuresis. Urine flow declined from 27.1 +/- 2.6 to 8.0 +/- 0.9 microliter/min/100 g body wt while sodium and potassium excretion were reduced 63 and 45%, respectively (P less than 0.01). Mean blood pressure and glomerular filtration rate were not significantly altered by aprotinin. Acute or chronic pretreatment with DOCA, to enhance kinin synthesis, failed to modify the renal excretory response to aprotinin suggesting that saline loading alone was able to induce kinin generation fully in these rats. The results indicate that aprotinin enhanced the reabsorption of filtrate in rats expanded with isotonic saline and imply an influence of renal kinins on the tubular transport of salt and water.     

Postnatal development of rat heart during 6-hydroxydopamine or propranolol treatment

Progressive postbirth development of mammalian heart contractile function is accompanied by augmentations of aerobic metabolic potential and cardiac myofibrillar ATPase activity. The temporal similarity of the above developmental sequences suggested that a single, unifying factor may coordinate myocardial maturation. It was hypothesized that cardiac sympathetic nervous system development might be regulating other aspects of myocardial growth. To test this hypothesis, previously well-defined aspects of heart metabolism and contractile protein ATPase activity were determined in rats which were either sympathectomized with 6-hydroxydopamine (6-OHDA) or subjected to chronic, beta-adrenergic blockade (propranolol) throughout the postbirth period from 3 to 6 weeks of age. Neither 6-OHDA treatment nor chronic, beta-adrenergic blockade resulted in a significant reduction of any metabolic enzyme specific activity or in myofibrillar ATPase. Myofibrillar creatine phosphokinase (CPK) activity underwent greater enhancement relative to ATPase during normal heart growth. Significant and divergent influences were exerted by 6-OHDA and propranolol drug regimens on myofibrillar CPK/ATPase enzyme activity ratio. These results indicate (a) the potential for independent regulation of myofibrillar CPK and ATPase, and (b) the advisability of evaluating CPK, ATPase, and CPK/ATPase enzymatic activities as myofibrillar correlates of heart contractile function. Nevertheless, the majority of developmentally related processes in the heart are minimally influenced by chemical sympathectomy.     

Effect of chemical sympathectomy on renal hydroelectrolytic handling in dogs with chronic caval constriction

The effect of renal selective chemical sympathectomy by intrarenal infusion of 6-hydroxydopamine (6-OHDA, 5 mg/kg body weight) on the renal excretion of water and electrolytes was studied in 7 dogs in whom a syndrome of sodium and water retention and ascites formation was induced by partial constriction of thoracic inferior vena cava. Propranolol (1 mg) and phentolamine (3 mg) were also injected to obviate acute systemic hemodynamic changes. Sympathectomy was performed once in 4 dogs and three times in 3 dogs. Sympathectomy induced an abrupt and transient increase in urinary flow (from 170 +/- 30 to 890 +/- 60 ml/24 h) and sodium excretion (from 4.5 +/- 1.5 to 178 +/- 21 mEq/24 h). This was accompanied by an important fall in plasma renin activity (from 2.2 +/- 0.2 to 0.5 +/- 0.1 ng angiotensin I/ml/h) and aldosterone, and disappearance of ascites. It is concluded that chemical sympathectomy, by increasing renal sodium and water excretion, mobilizes the ascites induced by chronic caval constriction, a fact that highlights the role of the renal sympathetic system in the pathogenesis of sodium and water retention by the kidney.     

Renal atrial natriuretic peptide receptors binding properties and function are resistant to DOCA-salt-induced hypertension in rats

Atrial natriuretic peptide receptor types A (NPR-A) and C (NPR-C) binding properties and functional characteristics in renal glomeruli have been investigated in deoxycorticosterone acetate (DOCA)-treated hypertensive Wistar-Kyoto (WKY) rats and their respective controls. We found that DOCA administration had no significant effect on the maximum binding capacity or the affinity of renal NPR-A and NPR-C. NPR-C is involved in the regulation of cAMP production. Our results indicate that the cAMP production by NPR-C is not altered in DOCA-induced hypertension, since ANP(1-28), CNP(1-22) and C-ANP, which specifically bind to NPR-C, show a similar inhibitory effect on cAMP production stimulated by the physiological agonist histamine in glomeruli from DOCA-treated rats and controls. Finally, we have found that DOCA-induced hypertension does not modify NPR-A or NPR-C expression in rat glomerular membranes. These findings indicate that NPR-A and NPR-C binding properties and NPR-C-mediated inhibition of cAMP generation remain unaltered in DOCA-treated rats.     

Delayed development of hypertension and increased aortic relaxation in spontaneously hypertensive rats after neonatal sympathectomy

The effect of neonatal sympathectomy on vasodilator responses to acetylcholine (ACh) and cAMP has been studied in aortic rings of spontaneously hypertensive rats (SHR) and normotensive animals. The relaxation of intact SHR aorta in response to ACh and cAMP was 20-35% lower than that of normotensive rats. Sympathectomy in normotensive rats did not affect the level of blood pressure and aorta reactivity to Ach. In SHR, sympathectomy caused a decrease in blood pressure, while relaxation in response to ACh and cAMP increased, as compared to intact SHR, but remained lower than in normotensive rats. The data obtained suggest that the decrease in arterial pressure of sympathectomized SHR is a result not only of the reduction in sympathetic effects but also of the increase in smooth muscle relaxation.     

Adrenocortical function in deoxycorticosterone acetate (DOCA)-hypertensive Yucatan miniature swine

Adrenocortical function was assessed in six normal and six chronic (greater than 12 weeks), DOCA-hypertensive Yucatan miniature swine; mean arterial pressures were 115.3 +/- 11.7 and 163.6 +/- 27.2 mm Hg, respectively (mean +/- SEM). Adrenocortical function was evaluated in vivo by measuring changes in plasma cortisol and aldosterone in response to exogenous ACTH (0.25 mg, iv), and in vitro by measuring the responses of collagenase-isolated adrenocortical cells to ACTH and angiotensin II. Corticoids were measured by specific radioimmunoassay. Basal plasma cortisol values of conscious DOCA-hypertensive swine were approximately 53% of the values of normotensive swine (P less than 0.05). However, ACTH induced a 419% increase in plasma cortisol values in DOCA-hypertensive swine compared to a 261% increase in the normotensive swine (P less than 0.05). These differences between the two groups were not altered by anesthesia. There were no significant differences in ACTH-induced changes in plasma aldosterone between the normotensive and DOCA-hypertensive swine. Experiments in vitro showed that the corticoid secretory responses of adrenocortical cells from DOCA-hypertensive animals were 6 times more sensitive to ACTH and 3.2 times more sensitive to angiotensin II than those of cells from normotensive swine. Thus, despite the possibility of adrenocortical insufficiency due to suppressed plasma renin activity and the negative feedback of DOCA on the hypothalamic-hypophyseal-adrenal axis, adrenocortical function of DOCA-hypertensive swine was hyperresponsive to trophic hormones. Results from this study suggest that the DOCA-hypertensive swine may be a valuable model in elucidating the relationship between hypertension and adrenocortical function and in investigating nonclassical control of the adrenal cortex, that is, control exerted during the hypertensive state that exists apart from or in addition to that exerted by ACTH and angiotensin II.     

Influence of enalapril on established pressure-overload cardiac hypertrophy in low and normal renin states in female rats

To determine whether effects of angiotensin converting enzyme (ACE) inhibitors on well-established pressure overload-induced cardiac hypertrophy and coronary remodeling depend upon normal plasma renin levels, the influence of enalapril on ventricular mass and coronary vascular resistance (CVR) was determined in a low-renin female rat model of chronic pressure overload, (deoxycorticosterone acetate hypertension, DOCA), and compared to its effect in a normal-renin model, (aortic construction, AC). Six weeks after experiment initiation, plasma renin activity of DOCA-treated rats was reduced to approximately 12% that of sham-treated and AC-treated groups. Enalapril was then added to the drinking water of half the animals in each group for two additional weeks. Comparing experimental groups to controls, this delayed enalapril treatment had 1) no effect on the elevated arterial pressures, 2) no effect on the elevated coronary resistance, and, in the DOCA group, 3) no effect on cardiac hypertrophy. However, this brief enalapril treatment reduced absolute and relative ventricular weights of AC rats. These data suggest that circulating renin is required for the anti-hypertrophic efficacy of late-onset brief treatment with enalapril. Since enalapril-induced reversal of cardiac hypertrophy in AC rats was not accompanied by reversal of coronary remodeling, growth signals other than angiotensin II may be involved in coronary remodeling.     

Differential Effects of Chemical Sympathectomy on Expression and Activity of Tyrosine Hydroxylase and Levels of Catecholamines and DOPA in Peripheral Tissues of Rats

Tyrosine hydroxylase (TH) mRNA and activity and concentrations of 3,4-dihydroxyphenylalanine (DOPA) and catecholamines were examined as markers of sympathetic innervation and catecholamine synthesis in peripheral tissues of sympathectomized and intact rats. Chemical sympathectomy with 6-hydroxydopamine (6-OHDA) markedly decreased norepinephrine and to a generally lesser extent TH activities and dopamine in most peripheral tissues (stomach, lung, testis, duodenum, pancreas, salivary gland, spleen, heart, kidney, thymus). Superior cervical ganglia, adrenals and descending aorta were unaffected and vas deferens showed a large 92% decrease in norepinephrine, but only a small 38% decrease in TH activity after 6-OHDA. Presence of chromaffin cells or neuronal cell bodies in these latter tissues, indicated by consistent expression of TH mRNA, explained the relative resistance of these tissues to 6-OHDA. Stomach also showed consistent expression of TH mRNA before, but not after 6-OHDA, suggesting that catecholamine synthesizing cells in gastric tissue are sensitive to the toxic effects of 6-OHDA. Tissue concentrations of DOPA were mainly unaffected by 6-OHDA, indicating that much of the DOPA in peripheral tissues is synthesized independently of local TH or sympathetic innervation. The differential effects of chemical sympathectomy on tissue catecholamines, DOPA, TH mRNA and TH activity demonstrate that these variables are not simple markers of sympathetic innervation or catecholamine synthesis. Other factors, including presence of neuronal cell bodies, parenchymal chromaffin cells, non-neuronal sites of catecholamine synthesis and alternative sources of tissue DOPA, must also be considered when tissue catecholamines, DOPA and TH are examined as markers of sympathetic innervation and local catecholamine synthesis.     

Effect of felodipine on renal hemodynamics and excretion in the dog

The effects of felodipine on renal hemodynamics and excretion were evaluated in the anesthetized dog. Unilateral renal arterial infusion of felodipine produced ipsilateral increases in the absolute and fractional excretion of sodium and water which were greater than those of potassium; these effects occurred in the absence of changes in mean arterial pressure, renal blood flow, or glomerular filtration rate. There were no significant effects on renal hemodynamic or excretory function in the contralateral kidney. The unilateral renal arterial infusion of isotonic saline or vehicle produced no significant effects on renal hemodynamic or excretory function in either ipsilateral or contralateral kidney. Felodipine, a calcium antagonist with vasodilator antihypertensive properties, in doses which do not affect systemic or renal hemodynamics in the dog, increased urinary flow rate and sodium excretion by decreasing renal tubular water and sodium reabsorption. As a vasodilator antihypertensive agent, felodipine possesses potentially advantageous diuretic and natriuretic properties.     

Electrophysiological effects of ouabain in 6-hydroxydopamine pretreated dogs

Chemical sympathectomy and bilateral vagotomy were used to evaluate the contribution of each division of the autonomic nervous system in the electrophysiological actions of ouabain. Intact and chemically sympathectomized dogs were given successive and cumulative doses of ouabain until toxicity became manifest (ventricular extrasystoles and (or) ventricular tachycardia). An additional group of normal and sympathectomized animals was also submitted to bilateral vagotomy in the presence of a therapeutic dose of ouabain. Sinus cycle length, AH interval of the His bundle electrogram, atrioventricular junctional effective and functional refractory periods were increased by ouabain at therapeutic doses. These effects were no different in sympathectomized dogs than in intact dogs, indicating the absence of any significant contribution of efferent sympathetic neural activity. However, our results suggested that vagal enhancement was the main mechanism whereby ouabain produced sinus bradycardia and depression of atrioventricular conduction. Sympathectomy with 6-OHDA did not modify nor abolish ouabain toxicity. However, toxic doses were significantly higher in sympathectomized animals than in normal animals. Considering that increasing heart rate by cardiac pacing or vagotomy significantly lowered toxic doses of ouabain in both intact and sympathectomized dogs, it is possible that sympathectomy could influence ouabain toxicity by altering heart rate alone.     

Pressure diuresis mechanism in the control of renal function and arterial pressure

Precise knowledge of the interrelationships between arterial pressure and urinary excretion of sodium and water is crucial to understanding the long-term control of arterial pressure. Although increases in renal perfusion pressure have been known for more than 35 years to inhibit tubular reabsorption, the mechanism of this pressure diuresis response, the humoral or physical factors involved, and even the nephron segments in which the changes in tubular function occur remain relatively unknown. This review focuses on the experimental evidence that supports current hypotheses concerning the mechanism of pressure diuresis. Specifically, it examines the possibility that pressure diuresis is caused by a small increase in glomerular filtration rate, alterations in the humoral or physical factors regulating proximal tubular reabsorption, and/or inhibition of tubular reabsorption in deep nephrons secondary to changes in hemodynamics in juxtamedullary nephrons. The concept originally proposed that the kidney serves as the dominant long-term controller of arterial pressure is largely based on the assumptions that the pressure diuresis phenomenon exists and that it occurs via a nonadaptive mechanism. It has been proposed that hypertension can develop only if the relationship between arterial pressure and sodium excretion is shifted toward higher pressures. The remainder of this review examines recent evidence indicating that an abnormality in the pressure natriuresis relationship may be associated with the development of hypertension in humans and in the genetic rat models of the disease.     

Effect of an exercise regimen on development of hypertension in rats

The possibility that a forced exercise regimen might prevent the development of hypertension induced in rats both by renal encapsulation and chronic administration of deoxycorticosterone acetate (DOCA) and NaCl has been studied. In renal hypertensive rats, forced exercise at 0.4 to 1.25 miles/day, 7 days/wk for 16-22 wk failed to prevent the development of hypertension and cardiomegaly and reduced renal concentrating ability accompanying the hypertension. In DOCA-treated rats (10 mg/wk), forced exercise at 0.4 and 0.8 mile/day, 7 days/wk for 16 wk also failed to prevent both the development of hypertension and cardiomegaly. A review of data of others reveals that exercise may delay the development of hypertension in both Dahl salt-sensitive and spontaneously hypertensive (SHR) rats and may modestly reduce the maximal level of pressure attained. Of the four models of hypertension studied to date in rats, the Dahl salt-sensitive strain appears to be the one that responded best to exercise, although blood pressure eventually reached that of sedentary controls.