摘要:

Delayed facilitation of norepinephrine release through the action of epinephrine (NE) at presynaptic beta-adrenoceptors has been postulated to account for the delayed hemodynamic effects of epinephrine and to be a mechanism causally related to the development of hypertension. To determine whether a short-term increase in epinephrine concentrations resulted in subsequent facilitation of sympathetic responses, 9 healthy subjects (age, 21 +/- 0.9 years) were studied at rest and during physiological stress on 2 occasions when they received an infusion of either saline or epinephrine (20 ng/kg per minute) in random order. Heart rate, blood pressure, forearm blood flow, epinephrine concentrations, and NE spillover were measured at rest, during mental stress (Stroop test), and during a cold pressor test. Measurements were performed before, during the 1-hour infusion of epinephrine or placebo, and 1 hour after the infusion. A radioisotope dilution method was used to measure NE spillover. Hemodynamic measurements and NE spillover were increased during the infusion of epinephrine, but 1 hour after discontinuation of epinephrine there was no significant augmentation of hemodynamic or sympathetic responses. NE spillover 1 hour after saline or epinephrine infusion was similar (0.85 +/- 0.2 versus 0.87 +/- 0.2 [micro sign]g/min; P=0.92). In addition, there was no delayed facilitation of stress-induced hemodynamic or NE responses after epinephrine. These findings do not support the hypothesis that epinephrine results in delayed facilitation of NE release. (Hypertension. 1998;32:1016-1021.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Moxonidine is an I1-imidazolinereceptor agonist that reduces blood pressure in hypertensives. Experimental data suggest that moxonidine inhibits central sympathetic activity. However, whether such a mechanism is involved in vivo in humans is still unclear. We investigated the effects of 0.4 mg moxonidine orally on muscle sympathetic nerve activity and heart rate in an open study in 8 healthy volunteers. Furthermore, we studied the effects of 0.4 mg moxonidine on muscle sympathetic nerve activity, heart rate, blood pressure, 24-hour blood pressure profile, and hormone plasma levels in 25 untreated hypertensives in a double-blind, placebo-controlled study. Moxonidine decreased muscle sympathetic nerve activity in both healthy volunteers (P<0.05 versus baseline) and hypertensives (P<0.02 versus placebo). Plasma norepinephrine also decreased (P<0.01), whereas plasma epinephrine and renin levels did not change (P=NS). Furthermore, moxonidine decreased systolic (P<0.0001) and diastolic (P<0.001) blood pressure. Heart rate decreased after moxonidine in healthy subjects (P<0.05); in hypertensives, heart rate decreased during the night hours (P<0.05) but not during daytime (P=NS). Plasma levels of LDL, HDL, and total cholesterol were not influenced by the drug (P=NS). Moxonidine decreases systolic and diastolic blood pressure by inhibiting central nervous sympathetic activity. This makes this new drug suitable for the treatment of human hypertension and possibly for other cardiovascular diseases with increased sympathetic nerve activity, ie, ischemic heart disease and heart failure. (Hypertension. 1998;32:1022-1027.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Dahl salt-sensitive (Dahl S) and salt-resistant (Dahl R) rats from 5 to 9 weeks of age received a regular or high salt diet and concomitantly an intracerebroventricular infusion of the angiotensin type 1 blocker losartan (1 mg [middle dot] kg-1[middle dot] d-1) or antibody Fab fragments, which bind ouabain and related steroids with high affinity, or gamma-globulins as control (200 [micro sign]g/d for both). At 9 weeks of age, blood pressure (BP), heart rate (HR), central venous pressure, and renal sympathetic nerve activity were recorded in conscious rats at rest and in response to air stress and to intracerebroventricular alpha2-agonistguanabenz (50 [micro sign]g) and ouabain (0.5 [micro sign]g). Baroreflex function was assessed by acute volume expansion with intravenous 5% dextrose and ramp changes of BP by +/- 50 mm Hg induced by intravenous phenylephrine and sodium nitroprusside. In Dahl S but not R rats, high salt significantly increased BP and HR; enhanced BP, HR, and renal sympathetic nerve activity responses to air stress and guanabenz; and attenuated cardiopulmonary and arterial baroreflex control of renal sympathetic nerve activity and HR. Both losartan and Fab fragments prevented these responses to high salt to a similar extent in Dahl S rats but had no effect in Dahl R rats on high salt. Sympathoexcitatory responses to ouabain were attenuated in Dahl S on high versus regular salt and were abolished in Dahl R or S treated with losartan or Fab fragments. Consistent with previous studies in SHR, the present data indicate that in Dahl S on high salt, both brain "ouabain" and angiotensin II contribute to decreased sympathoinhibition and increased sympathoexcitation, impairment of baroreflex, and therefore hypertension. (Hypertension. 1998;32:1028-1033.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

It has been shown that nitric oxide (NO) is synthesized in the central nervous system as well as in vascular endothelial cells. We recently reported that NO was involved in central cardiovascular regulation, modulated the baroreflex, and was involved in a reciprocal release with excitatory amino acids in the nucleus tractus solitarii (NTS) of rats. We also reported previously that adenosine increased the release of glutamate in the NTS. The purpose of the present study was to investigate the possible interaction of NO and adenosine in the NTS. Male Sprague-Dawley rats were anesthetized with urethane, and blood pressure was monitored intra-arterially. Unilateral microinjection of L-arginine (3.3 nmol/60 nL) into the NTS produced decreases in blood pressure and heart rate. Microinjection of adenosine (2.3 nmol/60 nL) also produced depressive and bradycardic effects. These cardiovascular effects were attenuated by prior administration of the specific adenosine receptor antagonist DPSPX (0.92 nmol). Similarly, prior administration of NO synthase inhibitor NG-monomethyl-L-arginineor NG-nitro-L-argininemethyl ester significantly attenuated the depressive and bradycardic effects of adenosine. These results demonstrate a reciprocal attenuation of adenosine receptor antagonist and NO synthase inhibitor on L-arginine and adenosine responses, respectively, in the NTS and implicate an interaction between NO and adenosine in central cardiovascular regulation. (Hypertension. 1998;32:1034-1038.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Patients with obstructive sleep apnea are at increased risk for hypertension. The mechanisms underlying this increased risk are not known. We tested the hypothesis that obstructive sleep apnea, independent of factors such as hypertension, obesity, and age, is characterized by impairment of baroreflex sensitivity. We measured muscle sympathetic nerve activity (MSNA) and heart rate responses to activation and deactivation of baroreceptors in newly diagnosed, never treated, normotensive patients with obstructive sleep apnea. These responses were compared with those obtained in healthy control subjects closely matched for age, body mass index, and blood pressure. Heart rate and MSNA changes during infusion of phenylephrine (baroreceptor activation) were similar in the control subjects and patients with sleep apnea. Infusion of nitroprusside (baroreceptor deactivation) elicited similar decreases in mean arterial pressure (MAP) but lesser MSNA increases in patients with sleep apnea than in control subjects. Calculation of Delta MSNA/Delta MAP ratio revealed that baroreflex regulation of sympathetic activity for similar blood pressure changes was diminished in patients with sleep apnea in comparison to normal control subjects (P=0.01). However, increases in heart rate during nitroprusside infusion were comparable in both groups. Sympathetic, blood pressure and heart rate responses to the cold pressor test were also similar in the 2 groups. Our results indicate that normotensive patients with sleep apnea have a selective impairment of the sympathetic response to baroreceptor deactivation but not to baroreceptor activation or to the cold pressor test. The impairment of baroreflex sympathetic modulation in patients with sleep apnea is not accompanied by any impairment of baroreflex control of heart rate. (Hypertension. 1998;32:1039-1043.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

We have used the apolipoprotein E (apoE)-deficient mouse model to determine whether both the angiotensin II type 1 (AT1) and the alpha1-adrenergicreceptors influence arteriosclerotic changes in this hyperlipidemic animal model. Mice were treated with antihypertensive drugs beginning at 9 weeks of age, and aortic atherosclerosis was measured after 12 weeks of treatment. Systolic blood pressure in the untreated apoE-deficient mouse averaged 104 mm Hg throughout the treatment period. Prazosin at a dose of 7.5 mg [middle dot] kg-1[middle dot] d-1was ineffective in attenuating atherosclerosis and did not significantly reduce blood pressure. Losartan, at dosages of either 20 or 30 mg [middle dot] kg-1[middle dot] d-1, also did not influence atherosclerosis and had only a slight blood pressure-lowering effect. However, combined treatment with both prazosin and losartan markedly reduced atherosclerotic lesion development from an average lesion size per section of 2.6 to 1.5 x 105[micro sign]m2(P<0.001) and significantly reduced blood pressure to 85 +/- 5 mm Hg. Treatment with NG-nitro-L-argininemethyl ester (40 mg [middle dot] kg-1[middle dot] d-1) produced significant elevations of blood pressure (127 +/- 3.8 mm Hg) but had no effect on the development of atherosclerosis. None of the treatments used affected plasma cholesterol throughout the 12-week period. These studies suggest that the vascular changes associated with atherosclerosis are influenced by a combination of AT1and alpha1-adrenergicreceptor activation. (Hypertension. 1998;32:1044-1048.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Dopamine, via D1-likereceptors, stimulates the activity of both protein kinase A (PKA) and protein kinase C (PKC), which results in inhibition of renal sodium transport. Since D1-likereceptors differentially regulate sodium transport in normotensive and hypertensive rats, they may also differentially regulate PKC expression in these rat strains. Thus, 2 different D1-likeagonists (fenoldopam or SKF 38393) were infused into the renal artery of anesthetized normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) (n=5 to 6/drug/strain). Ten or 60 minutes after starting the D1-likeagonist infusion, both the infused kidney and the noninfused kidney that served as control were prepared for analysis. The D1-likeagonists produced a greater diuresis and natriuresis and inhibited Na+,K+-ATPaseactivity in proximal tubule (PT) and medullary thick ascending limb (mTAL) to a greater extent in WKY (Delta 20 +/- 1%) than in SHR (Delta 7 +/- 1%, P<0.001). D1-likeagonists had no effect on PKC-alpha or PKC-lambda expression in either membrane or cytosol but increased PKC-theta expression in PT in both WKY and SHR at 10 minutes but not at 60 minutes. However, membranous PKC-delta expression in PT and mTAL decreased in WKY but increased in SHR with either 10 or 60 minutes of D1-likeagonist infusion. D1-likeagonists also decreased membranous PKC-zeta expression in PT and mTAL in WKY but increased it in PT but not in mTAL in SHR. We conclude that there is differential regulation of PKC isoform expression by D1-likeagonists that inhibits membranous PKC-delta and PKC-zeta in WKY but stimulates them in SHR; this effect in SHR is similar to the stimulatory effect of norepinephrine and angiotensin II and may be a mechanism for their differential effects on sodium transport. (Hypertension. 1998;32:1049-1053.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Dopamine and angiotensin II (Ang II) receptors have been reported to exhibit an interaction in renal proximal tubules. The present study was designed to investigate the regulation by a D2-likedopamine receptor of Ang II-mediated stimulation of Na,K-ATPase activity in the renal proximal tubules. Ang II (10-13to 10-9mol/L) stimulated Na,K-ATPase activity in the proximal tubules that was completely abolished when the tubules were pretreated with the D2-likereceptor agonist bromocriptine (1 [micro sign]mol/L) for 30 minutes. The effect of bromocriptine on Ang II response was prevented by domperidone (1 [micro sign]mol/L), a D2-likedopamine receptor antagonist. Similarly, the inhibition of forskolin (1 [micro sign]mol/L)-induced cAMP accumulation caused by Ang II (10 pmol/L) was also abolished in bromocriptine-pretreated tubules. Basal and forskolin-stimulated cAMP was not significantly different in bromocriptine-treated tubules compared with the control. [(3) H]-Ang II binding sites (angiotensin type 1 [AT1] receptors) were reduced by [almost equal to]65% in bromocriptine-treated proximal tubules, a result that was further substantiated by Western blot analysis revealing a 50% decrease in AT1receptors in bromocriptine-treated tubules compared with the control. Western blot analysis of G proteins revealed a 2-fold increase in Gsalpha and a 20% decrease in Gialpha 1 and Gialpha 2 in the bromocriptine-treated proximal tubules. Bromocriptine (1 [micro sign]mol/L) alone stimulated Na,K-ATPase activity during the first 30 minutes of incubation, and thereafter the stimulation fell to the basal level. Similarly, bromocriptine-mediated inhibition of cAMP lasted only up to 20 minutes. The data suggest that preactivation of D2-likedopamine receptors abolishes Ang II-mediated stimulation of Na,K-ATPase activity and inhibition of cAMP accumulation. This phenomenon may be a consequence of a decrease in AT1receptors and alterations in G protein levels in the proximal tubules. We propose that such a regulation of Ang II response by bromocriptine is the result of heterologous desensitization of the D2-likereceptor system. (Hypertension. 1998;32:1054-1059.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

60 [micro sign]m), intermediate (40 to 60 [micro sign]m), and distal (<40 [micro sign]m) ILAs. Myogenic responses were obtained by stepwise increase in perfusion pressure. Greater myogenic responsiveness was observed in ILAs with smaller diameters. Diltiazem (10 [micro sign]mol/L) inhibited myogenic responses of all segments of ILAs. Furthermore, gadolinium (10 [micro sign]mol/L), a mechanosensitive cation channel blocker, abolished myogenic responses of distal but not proximal ILA. In contrast, 2-nitro-4-carboxyphenyl-N, N-diphenyl-carbamate (200 [micro sign]mol/L), an inhibitor of phospholipase C, prevented myogenic responses of proximal but not distal ILA. Finally, basal proximal ILA diameters were increased by treatment with 50 nmol/L of staurosporine (P<0.05), and subsequent addition of thapsigargin (1 [micro sign]mol/L) blocked myogenic contraction of proximal ILAs. Myogenic responses of intermediate ILAs exhibited characteristics between those of distal and proximal ILAs. Our data indicate that underlying mechanisms for myogenic responses differ in distinct segments of ILAs. The present results suggest that mechanosensitive cation channels are involved in myogenic constriction of distal ILAs. Finally, our findings provide evidence that the stimulation of phospholipase C mediates myogenic contraction of proximal ILAs. (Hypertension. 1998;32:1060-1065.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Renal vascular reactivity is influenced by the level of dietary salt intake. Recent in vitro data suggest that afferent arteriolar contractility is modulated by extracellular chloride. In the present study, we assessed the influence of chloride on K+-inducedcontraction in isolated perfused rabbit afferent arterioles. In 70% of vessels examined, K+-inducedcontraction was abolished by acute substitution of bath chloride. Consecutive addition of Cl-(30, 60, 80, 100, 110, and 117 mmol/L) restored the sensitivity to K+, and half-maximal response was observed at 82 mmol/L chloride. The calcium channel antagonist diltiazem (10-6mol/L) abolished K+-inducedcontractions. Bicarbonate did not modify the sensitivity to chloride. Norepinephrine (10-6mol/L) induced full contraction in depolarized vessels even in the absence of chloride. Iodide and nitrate were substituted for chloride with no inhibitory effect on K+-inducedcontraction. Approximately 30% of the vessels constricted in response to K+in the absence of chloride. This response was reversibly blocked by the alpha1-blockerphentolamine (PA) (10-5mol/L) and, with PA present, the dependence on chloride was similar to the above series. The results show that K+-inducedcontraction of smooth muscle cells in the afferent arteriole is highly sensitive to chloride, whereas neurotransmitter release and ensuing contraction is not dependent on chloride. Thus, there are different activation pathways for depolarizing vasoconstrictors and for the sympathetic nervous system in renal afferent arterioles. This could be of physiological relevance for the resetting of afferent arteriolar sensitivity during changes in salt intake. (Hypertension. 1998;32:1066-1070.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID