Biomedical subjects

S Oparil

Publications and source records attributed to S Oparil.

At least 235 records · Page 13Linked to original sources

PubMed1987

The renal afferent nerves in the pathogenesis of hypertension.

The renal nerves play a role in the pathogenesis of hypertension in a number of experimental models. In the deoxycorticosterone acetate - salt (DOCA-NaCl) hypertensive rat and the spontaneously hypertensive rat (SHR) of the Okamoto strain, total peripheral renal denervation delays the development and blunts the severity of hypertension and causes an increase in urinary sodium excretion, suggesting a renal efferent mechanism. Further, selective lesioning of the renal afferent nerves by dorsal rhizotomy reduces hypothalamic norepinephrine stores without altering the development of hypertension in the SHR, indicating that the renal afferent nerves do not play a major role in the development of hypertension in this genetic model. In contrast, the renal afferent nerves appear to be important in one-kidney, one-clip and two-kidney, one-clip Goldblatt hypertensive rats (1K, 1C and 2K, 1C, respectively) and in dogs with chronic coarctation hypertension. Total peripheral renal denervation attenuates the severity of hypertension in these models, mainly by interrupting renal afferent nerve activity, which by a direct feedback mechanism attenuates systemic sympathetic tone, thereby lowering blood pressure. Peripheral renal denervation has a peripheral sympatholytic effect and alters the level of activation of central noradrenergic pathways but does not alter sodium or water intake or excretion, plasma renin activity or creatinine clearance, suggesting that efferent renal nerve function does not play an important role in the maintenance of this form of hypertension. Selective lesioning of the renal afferent nerves attenuates the development of hypertension, thus giving direct evidence that the renal afferent nerves participate in the pathogenesis of renovascular hypertension.

Afferent Pathways↗

PubMed1987

Failure of renal denervation to attenuate hypertension in Dahl NaCl-sensitive rats.

In previous experiments we have demonstrated that the renal nerves play a significant role in all genetic and (or) induced models of hypertension that we have studied. The current experiments extended this research by investigating the contribution of the renal nerves to hypertension in the Dahl NaCl-sensitive rat. This was investigated by assessing the effect of bilateral phenol renal denervation carried out prior to initiation of a high NaCl (8% NaCl) diet. In two separate studies, renal denervation did not affect systolic blood pressure in either Dahl NaCl-sensitive rats or their normotensive counterparts, Dahl NaCl-resistant rats. Further, denervation did not increase absolute urinary sodium excretion, percent urinary sodium excretion, urinary volume output, or food or water intake; nor did it differentially alter creatinine clearance or body weight. Denervation was verified at the termination of each study by a greater than 80% depletion of renal noradrenaline stores. These results indicate that the renal nerves do not provide a major contribution to hypertension in the Dahl NaCl-sensitive rat.

Aging↗

PubMed1987

Sympathetic function in spontaneously hypertensive rats after chronic administration of captopril.

The cardiovascular effects of electrical stimulation of the posterior hypothalamus, intravenous administration of norepinephrine (NE), and direct sympathetic nerve stimulation (SNS) were compared in spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY) given captopril (osmotic minipump, 1.25 micrograms/h icv) or vehicle for 4 wk beginning at age 7 wk. Mean arterial pressure (MAP) and renal and mesenteric flows (pulsed Doppler flow probes) were monitored in anesthetized rats. Following chronic administration of captopril the MAP was 141 +/- 4 mmHg in SHR receiving captopril and 183 +/- 6 mmHg in SHR receiving vehicle. Posterior hypothalamic stimulation, intravenous NE, and SNS resulted in lesser increases in MAP and renal and mesenteric vascular resistances in SHR treated with captopril. Response curves were shifted to the right, and the initial slopes and rate of change of slopes of the curves were less in captopril-treated SHR than vehicle-treated rats. The decrease in sensitivity to posterior hypothalamic stimulation was greater than the decrease in response to NE or SNS. The decrease in vascular reactivity in captopril-treated SHR was not due to increased sensitivity of the baroreflex for control of vascular resistance nor to a decrease in arterial pressure per se. WKY treated with captopril also showed lesser increases in MAP and renal and mesenteric vascular resistances in response to posterior hypothalamic stimulation, intravenous NE, and SNS. The depressor effects of intracerebroventricular captopril in SHR may be due, in part, to an attenuation in sympathetic vasoconstrictor tone. This attenuation involves both a decrease in vascular smooth muscle responsiveness to NE as well as a decrease in central stimulation of sympathetic outflow.

Animals↗

PubMed1987

Two renal alpha 2-adrenergic receptor sites revealed by p-aminoclonidine binding.

[3H]p-aminoclonidine [3H]PAC, a specific alpha 2-adrenergic agonist, was used to characterize alpha 2-adrenoceptor binding in rat renal membranes. Rosenthal plots demonstrated two binding sites with Kds of approximately 1.7 and 14.2 nM and Bmaxs (maximum binding) of 47.3 and 218.8 fmol/mg protein for the high- and low-affinity sites, respectively. These characteristics were confirmed by estimate of Kd parameters based on association and dissociation experiments. Pseudo-Hill coefficients generated from drug inhibition experiments were all less than unity, suggesting differential binding at two alpha 2-adrenoceptor binding sites. Specific alpha 2-adrenergic agonists exhibited greater binding affinity to both sites than did nonspecific drugs, and all drugs displayed greater affinity for the high- than the low-affinity binding site. Both guanyl nucleotides and sodium chloride inhibited [3H]PAC binding more at the high-affinity than at the low-affinity site. Renal denervation resulted in significant upregulation of receptor density only at the high-affinity sites with no change in receptor affinity at either site, suggesting that a majority of the alpha 2-adrenoceptors in the kidney are postsynaptic. Thus all lines of evidence in this study indicate that two alpha 2-adrenoceptor binding sites exist in the rat kidney.

Animals↗

PubMed1987

De novo intrarenal formation of angiotensin II during control and enhanced renin secretion.

In previous studies it has not been possible to determine net intrarenal formation of angiotensin II (ANG II) from arteriovenous ANG II concentrations because of the high intrarenal ANG II degradation rates (DR). This study was designed to determine ANG II-DR and to estimate net intrarenal ANG II formation during normal and enhanced renin secretion rate (RSR). In anesthetized dogs, plasma renin activity and ANG II were measured in arterial and renal venous blood by radioimmunoassay during four periods: control, renal arterial constriction (RAC), angiotensin converting enzyme (ACE) inhibition (MK 422), and MK 422 plus systemic arterial ANG II infusion. ANG II-DR was determined in each dog from the arterial-renal venous ANG II concentration difference during the period of ANG II infusion in the presence of ACE inhibition; this value was used to estimate net ANG II formation by predicting the amount of arterially delivered ANG II that escaped degradation. The average percent ANG II-DR calculated during ANG II infusion (range of 0.05 to 0.20 microgram/min) was 89 +/- 2%. In response to RAC, RSR increased from 11 +/- 3 to 24 +/- 5 ng ANG I X h-1 X min-1 X g-1. Arterial ANG II (67 +/- 11 pg/ml) and renal venous ANG II (29 +/- 6 pg/ml) increased to 133 +/- 18 and 61 +/- 10 pg/ml, respectively. Net intrarenal ANG II formation increased from 44 +/- 11 to 83 +/- 13 pg X min-1 X g-1 after renal arterial constriction. There was a significant relationship between the change in RSR and the change in ANG II formation rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMed1987

Hypoxia-induced inhibition of converting enzyme activity: role in vascular regulation.

Systemic and pulmonary vascular reactivity to graded doses of angiotensin I (ANG I), angiotensin II (ANG II), and, as a control, phenylephrine were examined in 14- or 28-day hypoxia-exposed and air control rats. Hypoxic rats exhibited pulmonary hypertension that was reversible on return to room air, but systemic arterial pressure was not altered by hypoxia. Systemic pressor responses to ANG I and ANG II were significantly less in the hypoxic rats than in the control rats at 14 and 28 days but returned to control levels in hypoxic animals that were then returned to room air, demonstrating reversibility of the hypoxia-induced changes in vascular reactivity. Pulmonary pressor responses to ANG I were significantly less at 14 days, whereas responses to ANG II were significantly greater at 28 days, in hypoxic rats than in controls. There were no significant differences in systemic and pulmonary pressor responses to phenylephrine between the hypoxic and air control animals. The altered systemic and pulmonary pressor responsiveness to ANG I and ANG II in hypoxic rats is probably related to mechanisms specific to the renin-angiotensin system, such as inhibition of intrapulmonary angiotensin-converting enzyme activity and down regulation of ANG II receptors in the systemic circulation. Further study is needed to elucidate these mechanisms.

Angiotensin I↗

PubMed1987

Renal catecholamines and alpha 2-adrenergic receptors in salt-related and genetic hypertension.

Increased dietary salt intake alters renal function which often leads to deleterious cardiovascular consequences. Studies were carried out to characterize the effects of high-salt diets on renal catecholamines and alpha 2-adrenergic receptors. These parameters were evaluated in both genetic and acquired forms of hypertension and also in normotensive rats on high-salt diets. Renal catecholamine content was determined by high-performance liquid chromatography with electrochemical detection. Renal alpha 2-adrenergic receptor-binding studies were performed on whole kidney homogenates using 3H-p-aminoclonidine to label both high- (0.5 nM) and low-affinity (5.0 nM) renal alpha 2-adrenergic receptors. Increased salt intake elevated blood pressure, decreased renal norepinephrine stores and resulted in renal alpha 2-adrenergic receptor up-regulation in deoxycorticosterone acetate salt hypertensive rats, Dahl-S rats and COX-SHR. The decreased renal stores of norepinephrine (NE) appeared to reflect increased renal NE utilization. In contrast, SHR (Charles River) had elevated NE stores and alpha 2-adrenergic receptors while on normal salt diets. Short-term (10-14 days) exposure to high-salt diets had modest effects in normotensive rats or COX-SHR, although it was sufficient to increase low affinity renal alpha 2-adrenergic receptor number. Renal dopamine metabolism was also altered by high-salt diets. These studies demonstrated a relationship between renal NE content and renal alpha 2-adrenergic receptors. The implications of this relationship and other salt-related changes in renal catecholamine metabolism were discussed as they pertained to hypertension and renal function.

Animals↗

PubMed1987

Continuous intravenous infusion of LY171555, a potent selective D2 receptor agonist, lowers blood pressure in the conscious rat.

Cardiovascular responses to sustained infusion of quinpirole (LY171555), a dopamine (DA) D2 receptor agonist, and bolus injection of quinpirole following sustained infusion were examined in conscious, unrestrained Sprague-Dawley rats to investigate the contributions of central and peripheral D2 receptors to the regulation of cardiovascular function. Continuous intravenous administration of quinpirole induced a transient pressor response followed by normalization of mean arterial pressure (MAP) and, at higher doses, a decrease in MAP below control levels. Intravenous bolus injections of quinpirole administered 30 min after termination of the infusion produced dose-dependent depressor responses which were blocked by pretreatment with domperidone, a peripheral D2 antagonist. The data suggest that continuous intravenous administration of quinpirole produces a transient centrally mediated pressor effect which is followed by a more sustained, peripherally mediated depressor response.

Animals↗

PubMed1987

Spontaneously hypertensive rats exhibit reduced hypothalamic noradrenergic input after NaCl loading.

Spontaneously hypertensive rats (SHR) of the Okamoto strain exhibit a significant exacerbation in severity of hypertension when fed diets high in NaCl. To examine the hypothesis that abnormalities in the monoaminergic innervation of the hypothalamus and brainstem contribute to the NaCl-induced exacerbation of hypertension, the monoamine and monoamine metabolite contents of specific hypothalamic and brainstem regions thought to be involved in the pathogenesis of hypertension were determined in SHR fed a diet containing 8% or 1% NaCl for either 2 or 6 weeks beginning at age 8 weeks. SHR maintained on the 8% NaCl diet for 2 weeks displayed significant decreases in norepinephrine in both the anterior and posterior hypothalamic regions but not in other brainstem or hypothalamic regions, as compared with animals consuming 1% NaCl. In addition, stores of the principal terminal norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol were reduced in the anterior hypothalamic region of SHR fed an 8% NaCl diet for 2 weeks. After 6 weeks on the diets, SHR fed 8% NaCl showed small but statistically nonsignificant reductions in norepinephrine stores of the anterior hypothalamic region as compared with SHR fed a basal diet, while WKY fed 8% NaCl had significantly elevated norepinephrine stores in the anterior hypothalamic region as compared with WKY fed a basal diet. There was a significant group X diet interaction (p less than 0.05). After 6 weeks on the 8% NaCl diet, SHR (but not WKY) displayed a significant reduction in norepinephrine content of the posterior hypothalamic region. No NaCl-induced differences in norepinephrine stores were found in the pons or medulla of either strain.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

PubMed1987

Exacerbation of hypertension by high chloride, moderate sodium diet in the salt-sensitive spontaneously hypertensive rat.

In salt-sensitive spontaneously hypertensive rats (SHR-S) of the Okamoto strain, dietary salt loading causes an exacerbation of hypertension that is associated with a decrease in noradrenergic input to the depressor neurons in the anterior hypothalamus. In the present study, the contribution of chloride to the salt-induced hypertensive response was examined in the SHR-S, in order to test the hypothesis that diets high in chloride but moderate in sodium elevate blood pressure in genetically predisposed subjects. SHR-S were fed diets high in NaCl (1.97% Na+, 2.93% Cl-; 5% NaCl), high in chloride (2.93%) but moderate in sodium (0.39%) or moderate in NaCl (0.39% Na+, 0.61% Cl-; 1% NaCl). After 2 weeks, rats on the high (5%) NaCl diet exhibited a significant elevation in blood pressure compared to rats on the moderate (1%) NaCl diet, and this elevation was maintained throughout the next 3 weeks. SHR-S on the high chloride diet were not significantly more hypertensive than 1% NaCl-fed SHR-S during the first 3 weeks, but during the fourth and fifth weeks, SHR-S on the high chloride diet displayed a significant exacerbation of hypertension. The diet-induced elevation in blood pressure in groups fed either the 5% NaCl or high chloride (compared to 1% NaCl) diets was associated with significant decreases in norepinephrine stores in the anterior hypothalamic region, but no other changes in monoamines or monoamine metabolites in this region or in the posterior hypothalamic region. The high chloride diet did not increase blood pressure in normotensive Wistar-Kyoto rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Hyperoxia-induced converting enzyme insufficiency in conscious rat: cardiovascular effects.

The effects of exposing rats to hyperoxia (100 percent O2) at normal atmospheric pressure for periods of 24-48 hours on components of the renin-angiotensin system and on blood pressure control were examined. Intrapulmonary conversion of angiotensin I (AI) to angiotensin (AII) was assessed using an isolated lung preparation perfused at constant flow. Exposure of rats to hyperoxia for 44-48 hours reduced single pass conversion of AI to AII in the pulmonary circulation from control levels of 82 +/- 4 to 29 +/- 5 percent (p less than 0.001). AII levels in trunk blood of 44-48 hour O2 exposed animals were 5.2 +/- 1.9 pg/ml, compared to 37.9 +/- 10.0 pg/ml in controls (p less than 0.001). Mean arterial pressure decreased significantly from 117 +/- 4.3 to 103 +/- 6.7 mmHg (p less than 0.05) in the O2 exposed group despite a threefold increase in plasma renin activity. The pressor response to exogenous AI was significantly diminished by O2 exposure, while the pressor response to exogenous AII remained unchanged from control. Pulmonary angiotensin-converting enzyme activity fell to approximately 50 percent of control in O2 exposed animals, but circulating converting enzyme activity was not change in this group. None of these alterations was apparent following 24 hours of hyperoxic exposure. These data suggest that O2 induced impairment in activity of angiotensin-converting enzyme at the endothelial membrane level has functionally significant effects on cardiovascular homeostasis, probably via reduced generation of endogenous AII.

Angiotensin I↗

PubMed1987

Hypertension produced by a high sodium diet in the borderline hypertensive rat (BHR).

The effect of high dietary sodium (8%) on blood pressure in spontaneously hypertensive (SHR), borderline hypertensive (BHR), and normotensive Wistar-Kyoto (WKY) rats was determined weekly by tail cuff plethysmography for one week of baseline and four weeks of diet. After 4 weeks, significant elevations in systolic blood pressure were found in SHR and BHR groups, but not in WKY. BHR studied an additional 4 weeks showed a further progression of hypertension, reaching levels nearly equal to control SHR. Direct measurement of arterial pressure in conscious animals in their home cage confirmed the elevation in pressure in both SHR and BHR groups. Metabolic studies revealed that the high sodium diet reduced body weight in SHR and BHR strains, but not in WKY. Although both urinary volumes and sodium excretion values were significantly lower in SHR and BHR compared with WKY, this effect disappeared when adjustments for body weight were made. Plasma norepinephrine determinations revealed a significant response to cold stress in all groups. Plasma epinephrine was elevated in all strains in response to cold stress; however, a consistent statistical elevation was seen only in WKY. The BHR is discussed as a model for determining the triggers responsible for environmentally-induced hypertension.

Animals↗

PubMed1987

Role of vasopressin in the cardiovascular effects of LY171555, a selective dopamine D2 receptor agonist: studies in conscious Brattleboro and Long-Evans rats.

To elucidate the role of central and peripheral arginine vasopressin (AVP) in the cardiovascular action of LY171555 in conscious rats, we have examined the effects of LY171555 on mean arterial pressure, heart rate, plasma AVP and catecholamine levels in conscious, congenitally AVP-deficient Brattleboro (DI) rats and Long-Evans (LE) control rats. Administration of LY171555 (1 mg/kg i.v.) increased heart rate without altering mean arterial pressure in DI rats but increased both mean arterial pressure and heart rate in LE rats. After pretreatment with domperidone, LY171555 induced both a pressure response and a tachycardia in DI rats. Domperidone pretreatment enhanced the pressor action of LY171555 and attenuated the LY171555-induced tachycardia in LE rats. After pretreatment with phenoxybenzamine, LY171555 induced a depressor and bradycardic response that could be blocked by pretreatment with domperidone in DI rats. Pressor and bradycardic responses to LY171555 were attenuated by phenoxybenzamine pretreatment in LE rats. LY171555 administration increased plasma norepinephrine and epinephrine levels in both DI and LE rats but increased plasma AVP only in LE rats. The vasopressor effect of the alpha-1 adrenoceptor agonist phenylephrine was significantly attenuated in DI rats compared with LE rats, whereas the pressor action of angiotensin II was similar in both groups. These results suggest that the pressor action of LY171555 in conscious LE rats is mediated by an increase in plasma AVP and by activation of sympathetic outflow through the central D2 dopaminergic system but not through the central vasopressinergic system.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMed1986

Increased vasopressinergic activity following DOCA administration in the rat.

The dynamics of hypothalamic arginine vasopressin (AVP) release was examined during the development of hypertension in rats with deoxycorticosterone (DOCA)-NaCL induced hypertension. Experiments were performed in four groups of uninephrectomized Sprague-Dawley rats 3, 7, 14 and 21 days after treatment with: (I) DOCA and 1% saline (DOCA-NaCl); (II) DOCA, regular chow, and tap water (DOCA-R-H2O); (III) regular chow and 1% saline (NaCl); and (IV) regular chow and tap water (H2O). Systolic blood pressure (BP) was significantly elevated in DOCA-NaCl and DOCA-R-H2O (183 +/- 5 and 155 +/- 4 mm Hg, respectively) but not in an additional control group which received DOCA and a low NaCl diet (119 +/- 2 mm Hg). Plasma AVP and hypothalamic AVP release were increased in all DOCA treated groups at each time point studied, while plasma osmolality was similar in each group. These studies demonstrate increases in the hypothalamic release of AVP in DOCA-NaCl hypertensive animals, but suggest that they are due to the mineralocorticoid and are independent of blood pressure and NaCl intake.

Animals↗

PubMed1986

Proteoglycans and hypertension. I. A biochemical and ultrastructural study of aorta glycosaminoglycans in spontaneously hypertensive rats.

The extracellular matrix of blood vessel walls contains elastin, collagen, and proteoglycans, all of which can affect vascular resistance and, hence, blood pressure by virtue of their biomechanical properties. In the present study, we have begun to explore the possibility that proteoglycans may play a role in the pathophysiology of hypertension by analyzing, qualitatively and quantitatively, the polysaccharide components of proteoglycans from aorta of two normotensive rat strains, Wistar Kyoto (WKY) and Wistar rats, and from spontaneously hypertensive (SH) rats of the Okamoto strain. The total concentration of aorta glycosaminoglycans in the SH rat was 33% higher than in the WKY rat, due to a 164% increase in chondroitin 4- and 6-sulfate. The content of dermatan sulfate (DS), hyaluronic acid (HA), and heparan sulfate (HS) was similar in the two strains. The 4-wk-old SH rat also had an increase in chondroitin sulfate (CS) compared to the 4-wk-old WKY rat, without any change in DS, HA, or HS. The Wistar rat had approximately the same concentration of CS und DS in the aorta as the WKY rat, but HS und HA were reduced by 62 and 37%, respectively. The galactosaminoglycans (CS and DS) were heterogeneous on cellulose acetate electrophoresis and exhibited a different pattern for each of the three strains. Undersulfated CS accounted for 15% of the total CS in WKY aorta but was present in only trace amounts in the SH aorta; 2% of the CS from the Wistar aorta was undersulfated. In all three strains, DS was exclusively 4-sulfated, and the CS contained approximately equal amounts of 4- and 6-sulfated galactosamine residues. Ultrastructural studies demonstrated that the HS was localized in the subendothelial matrix and the pericellular region surrounding the medial smooth muscle cells. CS and DS were primarily associated with collagen in the media. In the SH rat aorta the subendothelial matrix was thicker, and there was a relative increase in the CS/DS in the smooth muscle cell pericellular matrix. We suggest that, if similar alterations in CS proteoglycans are present in the resistance vessels, these changes may contribute to the increased peripheral vascular resistance in the hypertensive animal.

Animals↗

PubMed1986

The sympathetic nervous system in clinical and experimental hypertension.

In summary, many lines of evidence indicate that the sympathetic nervous system, via the renal nerves, plays an important role in the pathogenesis of renovascular hypertension in humans and laboratory animals. Patients with established renovascular hypertension have increased sympathetic nervous system activity, as evidenced by increased plasma and urinary norepinephrine levels, elevated excretion of catecholamine metabolites, and an exaggerated depressor response to centrally acting sympatholytic agents. The observation that converting enzyme inhibitors can cause both blood pressure and urinary norepinephrine excretion to return to normal in patients with renovascular hypertension is consistent with the interpretation that activation of the sympathetic nervous system in these subjects is, at least in part, angiotensin-induced. The sympathetic nervous system, via the efferent renal nerves, plays a role in the pathogenesis of hypertension in a number of experimental models. In the spontaneously hypertensive rat of the Okamoto strain (SHR) and in the DOCA/NaCl hypertensive model, increased renal efferent nerve activity contributes to the development of hypertension by causing increased renal sodium retention. In both of these experimental models, renal denervation delays the development and blunts the severity of hypertension. This delay is associated with increased urinary sodium excretion, suggesting a renal efferent mechanism. In contrast to the predominantly efferent renal nerve mechanisms observed in the DOCA-NaCl and SHR models, studies of the effects of renal denervation in one-kidney, one-clip and two-kidney, one-clip Goldblatt hypertensive rats suggest that renal afferent nerves are important in these models of hypertension. Total renal denervation in rats with established 1K, 1C and 2K, 1C hypertension attenuates the severity of the hypertension without altering sodium intake or excretion, renin activity, water intake, or renal function. Thus, efferent renal nerve activity does not appear to be involved in the development of maintenance of 1K, 1C or 2K, 1C hypertension. In contrast with the findings in SHR and DOCA-NaCl rats, these studies provide indirect evidence that the renal afferent nerves play a role in the pathogenesis of this form of experimental hypertension. The major effect of renal denervation in these models appears to be an interruption of renal afferent nerve activity, which by a direct feedback mechanism attenuates systemic sympathetic tone, thereby lowering blood pressure.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1986

Sensory denervation of the kidney attenuates renovascular hypertension in the rat.

To determine the role of the renal afferent nerves in the pathogenesis of one-kidney, one-clip renovascular hypertension, the renal afferent nerves were selectively lesioned by dorsal rhizotomy, a procedure that eliminates renal sensory input to the spinal cord but does not directly damage the sympathomotor innervation of the kidney. One week after denervation, the proximal left renal artery was clipped in denervated and sham control rats. Blood pressure of the sham group rose progressively over the next 5 wk, to 185 mmHg (systolic). In contrast, blood pressure of the denervated rats leveled off in the borderline hypertensive range, a level significantly lower than that of the sham group but significantly higher than that of non-clipped rats. In two further experiments the specificity of this effect was demonstrated. Lesion of the dorsal root nerves on the side of nephrectomy did not significantly lower blood pressure of non-clipped rats, and contralateral dorsal rhizotomy did not lower the blood pressure of clipped rats. These results demonstrate that the renal afferent nerves significantly contribute to one-kidney, one-clip renovascular hypertension in the rat.

Afferent Pathways↗

PubMed1986

Angiotensin extraction by trout tissues in vivo and metabolism by the perfused gill.

Plasma clearance and tissue accumulation of 125I-angiotensin I, [Asp1, Ile5]ANG I, and [14C]sucrose, an inert volume reference, were measured after a bolus injection into the dorsal aorta of rainbow trout, Salmo gairdneri. Retention and metabolism of ANG I to angiotensin II (ANG II) and their constituent 1-4 peptide by the gill were examined using an isolated perfused arch preparation in which outflow from the respiratory and central filamental (venous) pathways was separated. Clearance of ANG I from plasma is multiexponential, reflecting dilution and tissue extraction. Liver, bile, gonads, corpuscles of Stannius, and white skeletal muscle accumulate more 125I than 14C; gill tissue accumulates less 125I than 14C. ANG I and II are retained by the perfused gill longer than the inert vascular marker sucrose, even though the distribution volumes of the former are less. The gill respiratory pathway converts ANG I to ANG II whereas the venous pathway metabolizes either ANG I or II to the 1-4 peptide and other metabolites. The gill respiratory pathway is in series with the systemic vasculature, has a large blood-cell contact area, and, like the mammalian lung, is ideally suited to activate ANG I. The gill venous pathway is in parallel with the systemic vasculature and removes ANG II from the circulation. During stress, elevated plasma catecholamines may reduce venous perfusion and thereby help maintain elevated circulating ANG II levels through reduced venous metabolism.

Angiotensin I↗