Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The acute effects of physiological levels of AVP and oxytocin administration on renal water and sodium handling have been investigated in New Zealand genetically hypertensive and normotensive rats. AVP infusion was associated with an antidiuresis in both normotensive and hypertensive rats and while normotensive rats also displayed a dose-related natriuresis, this was attenuated in hypertensive rats. Oxytocin administration had no effect on urine flow or sodium excretion in normotensive rats, but was associated with an antidiuresis in hypertensive rats. Combined hormone infusion produced a greater reduction in urine flow than following AVP alone in both normotensive and hypertensive groups and was associated with a potentiation of the natriuretic action of AVP in the hypertensive animals. The data suggest that the contribution of oxytocin to renal sodium excretion in hypertensive rats may be suppressed. A compensatory increase in basal AVP secretion in hypertensive rats may overcome their apparent renal insensitivity to AVP, to maintain appropriate sodium excretion. This intriguing disturbance in neurohypophysial function may reflect or possibly contribute to the hypertension of these animals.
 ...
PMID:Neurohypophysial hormone influence on renal function in the New Zealand genetically hypertensive rat. 339 74

Arginine vasopressin (AVP) was infused into the renal artery of seven uninephrectomized conscious dogs at successive rates of 0.09, 0.36, and 1.46 ng X kg-1 X min-1 for 18, 9, and 5 days, respectively; subsequently, the nonpressor analogue of AVP, 1-desamino-8-D-arginine vasopressin (DDAVP), was infused intrarenally for 7 additional days. The lowest infusion rate of AVP produced a high concentration of AVP in the renal circulation (maximal antidiuresis) with only a relatively moderate increase in peripheral plasma AVP concentration. For comparison, the effects of a comparable increase in peripheral plasma AVP concentration during intravenous infusion at this same rate were observed in an additional group of dogs. Acutely, when this low dose of AVP was infused either intrarenally or intravenously, there was marked antidiuresis, but there were no significant changes in mean arterial pressure (MAP), renal hemodynamics, or urinary electrolyte excretion. Chronically, in both groups of animals, cumulative water balance was positive, and glomerular filtration rate, effective renal plasma flow, and MAP (16-18 mmHg) all increased; plasma renin activity decreased. Similar changes were observed during DDAVP infusion. When elevated peripheral plasma levels of AVP were achieved during the higher infusion rates of AVP, natriuresis and diuresis occurred, but, otherwise there was little change in the above variables, including MAP. Thus the hydrosmotic effects of AVP appear to account for its moderate hypertensive activity. Further, the failure of AVP to produce prominent hypertension, even when pronounced systemic vasoconstrictor effects are manifested, may be a result of its inability to promote significant renal vasoconstriction and antinatriuresis.
 ...
PMID:Cardiovascular and renal responses to chronic vasopressin infusion. 351 69

The two major biological actions of vasopressin are antidiuresis and vasoconstriction. The antidiuretic action of low concentrations of vasopressin is well established and concentrations 10 to 100 times above those required for antidiuresis elevate arterial blood pressure. Antidiuresis is mediated by V2-receptors at the kidney, whereas vasopressin constricts arterioles by binding at V1-receptors. Pharmacological effects of specific antagonists of the vasoconstrictor activity of vasopressin (vascular or V1-receptor antagonists) are presented. Low concentrations of vasopressin do have significant hemodynamic effects. Physiological concentrations of vasopressin cause vasoconstriction and elevate systemic vascular resistance. In subjects with intact cardiovascular reflex activity, however, cardiac output falls concomitantly and blood pressure therefore does not change. In animals with baroreceptor deafferentation or in patients with blunted baroreceptor reflexes (autonomic insufficiency) a rise in plasma vasopressin causes vasoconstriction and an increase in blood pressure, because cardiac output does not fall under these conditions. Vasopressin contributes substantially via increase in systemic vascular resistance to maintain blood pressure during water deprivation. During hemorrhage and hypotension vasopressin has a major role to restore blood pressure. In experimental hypertension vasopressin contributes to the development and maintenance of high blood pressure in DOCA, but not in genetic hypertensive rats. The role of vasopressin in human hypertension is not yet clear. Vasopressin in extrahypothalamic areas of the brain affects circulatory regulation by interaction with central cardiovascular control centers. The exact mechanism of how vasopressin is involved in central regulation of blood pressure remains to be established. In contrast to our previous opinion vasopressin is a vasoactive hormone also at low plasma concentrations. Its cardiovascular action is more complex than previously assumed.
 ...
PMID:[Cardiovascular effect of the antidiuretic hormone arginine vasopressin]. 406 6

7 hypertensive patients (H) and 8 normotensive volunteers (N) were loaded with NaCl (4.5 mEq Na +/kg body weight i.v.) during water diuresis (A) and antidiuresis (B). In 6 antidiuretic subjects (3H and 3N) urine volume (V) was progressively raised up to over 30 ml/min, by intravenous infusion (12 ml/min) of hypertonic (3%) saline (C). It is assumed that in (A) CH2O is an index of Na+ reabsorption in short Henle's loops. In (B) and (C) TcH2O is proportional to Na+ reabsorption in long Henle's loops. In (A) CcH2O was significantly lower in H. In (B) TcH2O was similar in H and N. In (C), TcH2O reached an earlier plateau in H than in N. These results demonstrate that exaggerated natriuresis depends on defective Na+ reabsorption in Henle's loops, suggesting that the defect depends upon the transmission of hypertension to medullary circulation. The increase in hemodynamic pressure in vasa recta opposes Na+ reabsorption both in short and in long Henle's loops. However, the effects on TcH2O of the decrease in Na+ reabsorption in long loops is blunted by the greater Na+ delivery, secondary to the increase in GFR, that follows the rise in filtration pressure.
 ...
PMID:Exaggerated natriuresis in the hypertensive man: clinical evidence for intrarenal hemodynamic heterogeneity. 721 42

We have studied the sequential effects of cyclosporine during the first four days after its initiation in an effort to elucidate the primary and secondary events in the pathogenesis of cyclosporine induced nephrotoxicity and hypertension. Knowledge about the earliest effects of cyclosporine provides a more logical approach for devising therapeutic strategies to counteract nephrotoxicity and hypertension. On day 1, cyclosporine acutely increased systemic BP and decreased urine volume. Plasma renin activity was suppressed by day 2 and remained so thereafter. Renal sodium excretion was not affected until day 4 at which point a natriuresis occurred. Cyclosporine exerted a more marked antidiuretic effect on day 4 compared to day 1, which was augmented by a physiological infusion of vasopressin. Over the first four days of therapy, glomerular filtration rate and effective renal plasma flow were unchanged. Our data show that cyclosporine induced hypertension in the initial stages is not sodium dependent, and that changes in renal water handling were not dependent on alterations in the glomerular filtration rate or effective renal plasma flow. In fact, a natriuresis occurred which was most likely due to a combination of pressure natriuresis and angiotensin II suppression. The cyclosporine induced antidiuresis may indicate a distal nephron effect since cyclosporine augmented the antidiuretic effect of vasopressin, although vasopressin levels per se were not increased by cyclosporine alone.
 ...
PMID:Sequential effects of cyclosporine therapy on blood pressure, renal function and neurohormones. 800 92

In this study we evaluated the possibility that angiotensin-(1-7) [Ang-(1-7)] acts as an endogenous osmoregulatory peptide by determining the effect of acute administration of its selective antagonist [D-Ala7]Ang-(1-7) (A-779) on renal function parameters in rats. In addition, we investigated the physiological mechanisms involved in the antidiuretic effect of Ang-(1-7). The antidiuretic effect of Ang-(1-7) (40 pmol/0.05 mL per 100 g BW) in water-loaded rats was completely blocked by A-779 (vehicle-treated, 3.34 +/- 0.43 mL/h; Ang-(1-7), 1.48 +/- 0.23; A-779, 2.72 +/- 0.35; Ang-(1-7) plus A-779, 3.26 +/- 0.49). In contrast, the antidiuretic effect of Ang-(1-7) was not significantly changed by a vasopressin V2 receptor antagonist in a dose that completely blocked the antidiuresis produced by an equipotent dose of vasopressin. In addition, Ang-(1-7) administration did not significantly change vasopressin plasma levels in water-loaded rats. The antidiuretic effect of Ang-(1-7) in water-loaded rats was associated with a reduction of creatinine clearance (0.68 +/- 0.04 versus 1.38 +/- 0.32 mL/min in vehicle-treated rats, P <.05) and an increase in urine osmolality (266.8 +/- 32.7 versus 182.8 +/- 14 mOsm/kg in vehicle-treated rats, P <.05). An effect of Ang-(1-7) in tubular water transport was demonstrated in vitro by a fourfold increase in the hydraulic conductivity of inner medullary collecting ducts in the presence of 1 nmol/L Ang-(1-7). Subcutaneous administration of A-779 (2.3 to 9.2 nmol/100 g) produced a significant increase in urine volume (4.6 nmol/100 g, 0.45 +/- 0.12 mL/h; vehicle-treated rats, 0.16 +/- 0.03 mL/h; P <.05) comparable to that of acute administration of a vasopressin V2 receptor antagonist. The diuretic effect of A-779 was associated with an increase in creatinine clearance and decrease in urine osmolality. In contrast, no significant effects on urine volume were observed after systemic administration of angiotensin subtype 1 or 2 receptor antagonists (DuP 753 and CGP 42112A, respectively). These findings suggest that endogenous Ang-(1-7), acting on specific receptors, participates in the control of hydroelectrolyte balance by influencing especially water excretion.
Hypertension 1996 Apr
PMID:Evidence for a physiological role of angiotensin-(1-7) in the control of hydroelectrolyte balance. 861 63

Bradykinin and lys-bradykinin generated intrarenally appear to be important renal paracrine hormones. However, the renal effects of endogenously generated bradykinin are still not clearly defined. In this study, we measured acute changes in renal excretory and hemodynamic functions and renal cortical interstitial fluid levels of bradykinin, prostaglandin E2, and cGMP in response to an acute intrarenal arterial infusion of the bradykinin B2 receptor antagonist Hoe 140 (icatibant), cyclooxygenase inhibitor indomethacin, or nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) given individually or combined in uninephrectomized, conscious dogs (n=10) in low sodium balance. Icatibant caused a significant decrease in urine flow, urinary sodium excretion, and renal plasma flow rate (each P<.001). Glomerular filtration rate did not change during icatibant administration. Icatibant produced an unexpected large increase in renal interstitial fluid bradykinin (P<.0001) while decreasing renal interstitial fluid prostaglandin E2 and cGMP (each P<.001). Both indomethacin and L-NMMA when given individually caused significant antidiuresis and antinatriuresis and decreased renal blood flow (each P<.001). Glomerular filtration rate decreased during L-NMMA administration (P<.001) and did not change during indomethacin administration. Combined administration of icatibant and indomethacin or L-NMMA caused significant decreases in renal excretory and hemodynamic functions, which were not different from changes observed with icatibant alone. The failure of icatibant to change renal function after inhibition of cyclooxygenase and nitric oxide synthase activity suggests that the effects of kinin B2 receptor are mediated by intrarenal prostaglandin E2 and nitric oxide generation. The increase in renal interstitial fluid bradykinin during icatibant requires further study of possible alterations in kinin synthesis, degradation, or clearance as a result of B2 receptor blockade.
Hypertension 1997 Mar
PMID:Bradykinin B2 receptor modulates renal prostaglandin E2 and nitric oxide. 905 92

The aim of this investigation was to compare the contribution of brain angiotensin II in mediating the transmission of a somatosensory stimulus within the brain to generate a renal sympathetic nerve-dependent antidiuresis and antinatriuresis in normotensive Wistar rats and stroke-prone spontaneously hypertensive rats (SHRSP). In anesthetized Wistar rats, stimulation of somatosensory receptors by subcutaneous capsaicin increased blood pressure by 9%, had no effect on renal hemodynamics, but decreased urinary flow and sodium excretion by 30% to 40%. These antidiuretic and antinatriuretic, but not blood pressure, responses were absent after intracerebroventricular losartan administration to block angiotensin II type 1 receptors. By contrast, in the SHRSP, although subcutaneous capsaicin raised blood pressure and renal blood flow, neither glomerular filtration rate, urinary flow, nor sodium excretion changed, and this pattern of responses was unaffected after intracerebroventricular losartan. However, an intracerebroventricular infusion of angiotensin II increased basal blood pressure and fluid output, and the capsaicin challenge elicited vasopressor, antidiuretic, and antinatriuretic responses similar in magnitude to those observed in the Wistar rats. The capsaicin challenge in the SHRSP also caused a slowly developing, long-lasting fall in blood pressure and fluid excretion. These findings show that angiotensin II is a necessary component in the somatorenal reflex in normotensive rats but that endogenous angiotensin II is unable to exert this role in SHRSP.
Hypertension 2001 Jun
PMID:Role of brain angiotensin II on somatosensory-induced antinatriuresis in hypertensive rats. 1140 79

Blood pressure variability is buffered by at least two mechanisms: the arterial baroreceptor reflex and nitric oxide (NO). Only recently is the importance of blood pressure variations on cardiovascular control being investigated. Here we report of a study performed in conscious dogs, in which renovascular hypertension was induced. Reduction of renal arterial pressure (RAP) to 85 mmHg for 24 h elicited profound hypertension by 60 mmHg (vs. control: 110 +/- 3 mmHg; P < 0.01). This was accompanied by reduced volume and sodium excretion (-48% of control, P < 0.01 and -80% of control, P < 0.01, respectively) and augmented renin release by more than two-fold (P < 0.01). This intervention was compared with a protocol in which RAP was reduced to the same mean value, however, RAP oscillated by +/-10 mmHg at 0.1 Hz. This manoeuvre led to a transient increase in NO3 excretion in urine (P < 0.01), blunted antidiuresis (-14% of control) as well as antinatriuresis (-40% of control) and attenuated the increased renin release by 30% (P < 0.05). In consequence, the magnitude of blood pressure increase was only half as high as that observed during static reduction of RAP (P < 0.01). It is concluded that blood pressure oscillations to the kidney have a profound influence on water and electrolyte balance and on renin release, which alleviates the onset of Goldblatt hypertension.
 ...
PMID:Nitric oxide and the role of blood pressure variability to the kidney. 1167 25

The aim of the present study was to distinguish between the direct effects of the renal nerves on renal function and indirect effects via neurally mediated increased systemic angiotensin II. We applied low-level electrical stimulation (1 Hz) to the left renal nerves in pentobarbitone-anesthetized rabbits for 180 minutes and measured renal blood flow, sodium excretion, and urine flow rate from both the stimulated and the nonstimulated contralateral kidney in the presence and the absence of ACE inhibition (enalaprilat). Stimulation resulted in an angiotensin II-mediated rise in arterial pressure and decreases in renal blood flow, urine flow rate, and sodium excretion on the stimulated side. On the nonstimulated denervated side, we found no change in renal blood flow, but found a decrease in urine flow rate. With ACE inhibition, renal stimulation no longer caused an increase in arterial pressure, the antidiuretic responses of the stimulated kidney were attenuated, and, importantly, the decrease in urine flow rate on the nonstimulated kidney was completely abolished. We therefore propose that although a direct effect of the renal nerves on sodium excretion is clearly present, the antidiuresis and antinatriuresis observed during renal activation is further supported by a neurally mediated increase in systemic angiotensin II.
Hypertension 2003 Mar
PMID:Role of angiotensin II in the neural control of renal function. 1262 63


<< Previous 1 2 3 Next >>