Sympathetic Vasoconstriction as a Mechanism of Action of Ouabain in Forearm Arterioles of Hypertensive Patients

1989 ◽  
Vol 77 (5) ◽  
pp. 541-545 ◽  
Author(s):  
Roberto Pedrinelli ◽  
Stefano Taddei ◽  
Antonio Salvetti
Keyword(s):  
Blood Flow ◽  
Neurotransmitter Release ◽  
Forearm Blood Flow ◽  
Specific Effect ◽  
Systemic Arterial Pressure ◽  
Vascular Effect ◽  
Uncomplicated Hypertension ◽  
Adrenoceptor Antagonist ◽  
Postsynaptic Site ◽  
Pre Treatment

1. The interaction of ouabain, a Na+/K+ adenosine 5′-triphosphatase inhibitor, with sympathetic mechanisms of vasoconstriction, as well as its possible site(s) of action, were investigated in forearm arterioles of patients with uncomplicated hypertension. 2. Intra-arterial infusion of ouabain per se decreased forearm blood flow without changes in systemic arterial pressure or contralateral flow. However, the vasoconstrictor effect of the glycoside was abolished after local pre-treatment with either phentolamine, a competitive α-adrenoceptor antagonist, or bretylium tosylate, a neurotransmitter blocker. 3. To exclude a non-specific effect due to the vasodilatation, a similar protocol was performed using histamine, which acts independently of sympathetic mechanisms. The vascular effect of ouabain was maintained in spite of histamine-induced increases in forearm blood flow even greater than those obtained from either blocker. 4. To discriminate between pre- and post-synaptic site(s) of action of ouabain, exogenous noradrenaline was infused intra-arterially after inactivation of local neurotransmitter release by bretylium, thus causing direct postsynaptic vascular α-adrenoceptor stimulation. Under these conditions, noradrenaline decreased forearm blood flow irrespective of the presence or absence of ouabain. 5. Thus, local sympatholysis by drugs acting on different levels of the sympathetic neuroeffector junction abolished the effect of ouabain, whereas histamine did not influence it. The data provide positive evidence for an effect of ouabain on sympathetically mediated vasoconstriction. This action is apparently not exerted at a postsynaptic site but possibly by enhancing neurotransmitter release. 6. If a circulating endogenous ouabain-like Na+/K+ adenosine 5′-triphosphatase inhibitor is relevant to the development of hypertension in man, it might act through a similar mechanism.

scholarly journals New-Onset Diabetes, Endothelial Dysfunction, and Cardiovascular Outcomes in Hypertensive Patients: An Illness-Event Model Analysis

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 721
Author(s):  
Raffaele Maio ◽  
Edoardo Suraci ◽  
Benedetto Caroleo ◽  
Cristina Politi ◽  
Simona Gigliotti ◽  
...  
Keyword(s):  
Blood Flow ◽  
Endothelial Dysfunction ◽  
Confidence Interval ◽  
Cardiovascular Events ◽  
Forearm Blood Flow ◽  
Cardiovascular Outcomes ◽  
Hazard Ratio ◽  
Baseline Status ◽  
Event Model ◽  
New Onset

Background. Insulin resistance and endothelial dysfunction are common findings in hypertensives, both predisposing to a higher risk of diabetes and cardiovascular events. We designed this study to evaluate the role of endothelial dysfunction in three pathogenetic pathways: (1) from baseline to cardiovascular events, (2) from baseline to diabetes, and (3) from new-onset diabetes to cardiovascular events. Methods. We enrolled 653 Caucasian never-treated hypertensives. Endothelial dysfunction was investigated by strain-gauge plethysmography; incident diabetes and cardiovascular events were evaluated by an illness-event model analysis. Results. During the follow-up (median 113 months), we documented 191 new cardiovascular events and 92 new cases of diabetes. In a multiple Cox regression analysis, acetylcholine-stimulated forearm blood flow [100% decrease, hazard ratio: 2.42 (95% confidence interval = 1.72–3.40)] and serum high-sensitivity C-reactive protein [hazard ratio: 1.30 (95% confidence interval = 1.21–1.40)] had an independent association with cardiovascular outcomes. The incidence rate of cardiovascular outcomes in diabetes-developer patients was higher than in the diabetes-free ones (34.9 vs. 2.5 events per 100 persons-year). In an illness-event model, a 100% decrease in forearm blood flow was associated with a 55.5% hazard ratio increase (hazard ratio: 1.56, 95% confidence interval: 1.33–1.82) of transition 1 (from baseline status to cardiovascular events) and to an almost doubled increase (hazard ratio: 2.54, 95% CI: 2.00–3.25) of the risk of transition 2 (from baseline status to diabetes). No such effects were found in transition 3 (from diabetes to cardiovascular events). Conclusions. Endothelial dysfunction plays a primary role in the pathways leading to diabetes and cardiovascular events in hypertensives. When diabetes is overt, endothelial dysfunction has no predictive value for subsequent cardiovascular events.

Failure of prostaglandins to modulate the time course of blood flow during dynamic forearm exercise in humans

1996 ◽  
Vol 81 (4) ◽  
pp. 1516-1521 ◽  
Author(s):  
J. K. Shoemaker ◽  
H. L. Naylor ◽  
Z. I. Pozeg ◽  
R. L. Hughson
Keyword(s):  
Blood Flow ◽  
Brachial Artery ◽  
Time Course ◽  
Forearm Blood Flow ◽  
Voluntary Contraction ◽  
Double Blind ◽  
Rate Of Increase ◽  
Forearm Exercise ◽  
Blind Manner ◽  
Exercise In Humans

Shoemaker, J. K., H. L. Naylor, Z. I. Pozeg, and R. L. Hughson. Failure of prostaglandins to modulate the time course of blood flow during dynamic forearm exercise in humans. J. Appl. Physiol. 81(4): 1516–1521, 1996.—The time course and magnitude of increases in brachial artery mean blood velocity (MBV; pulsed Doppler), diameter ( D; echo Doppler), mean perfusion pressure (MPP; Finapres), shear rate (γ˙ = 8 ⋅ MBV/ D), and forearm blood flow (FBF = MBV ⋅ π r 2) were assessed to investigate the effect that prostaglandins (PGs) have on the hyperemic response on going from rest to rhythmic exercise in humans. While supine, eight healthy men performed 5 min of dynamic handgrip exercise by alternately raising and lowering a 4.4-kg weight (∼10% maximal voluntary contraction) with a work-to-rest cycle of 1:1 (s/s). When the exercise was performed with the arm positioned below the heart, the rate of increase in MBV and γ˙ was faster compared with the same exercise performed above the heart. Ibuprofen (Ibu; 1,200 mg/day, to reduce PG-induced vasodilation) and placebo were administered orally for 2 days before two separate testing sessions in a double-blind manner. Resting heart rate was reduced in Ibu (52 ± 3 beats/min) compared with placebo (57 ± 3 beats/min) ( P < 0.05) without change to MPP. With placebo, D increased in both arm positions from ∼4.3 mm at rest to ∼4.5 mm at 5 min of exercise ( P < 0.05). This response was not altered with Ibu ( P > 0.05). Ibu did not alter the time course of MBV or forearm blood flow ( P > 0.05) in either arm position. The γ˙ was significantly greater in Ibu vs. placebo at 30 and 40 s of above the heart exercise and for all time points after 25 s of below the heart exercise ( P < 0.05). Because PG inhibition altered the time course ofγ˙ at the brachial artery, but not FBF, it was concluded that PGs are not essential in regulating the blood flow responses to dynamic exercise in humans.

Effects of nipradilol, a new nitroester-containing beta-blocker, on forearm blood flow

1992 ◽  
Vol 52 (4) ◽  
pp. 587-592 ◽  
Author(s):  
Shigeki Akabane ◽  
Shigehiro Katayama ◽  
Akira Itabashi ◽  
Munemichi Inaba ◽  
Yoshiko Maruno ◽  
...  
Keyword(s):  
Blood Flow ◽  
Beta Blocker ◽  
Forearm Blood Flow

Influence of graded dehydration on hyperthermia and cardiovascular drift during exercise

1992 ◽  
Vol 73 (4) ◽  
pp. 1340-1350 ◽  
Author(s):  
S. J. Montain ◽  
E. F. Coyle
Keyword(s):  
Blood Flow ◽  
Prolonged Exercise ◽  
Forearm Blood Flow ◽  
Sweat Rate ◽  
Sodium Concentration ◽  
O2 Consumption ◽  
Esophageal Temperature ◽  
Warm Environment ◽  
Cardiovascular Drift ◽  
Highly Correlated

This investigation determined the effect of different rates of dehydration, induced by ingesting different volumes of fluid during prolonged exercise, on hyperthermia, heart rate (HR), and stroke volume (SV). On four different occasions, eight endurance-trained cyclists [age 23 +/- 3 (SD) yr, body wt 71.9 +/- 11.6 kg, maximal O2 consumption 4.72 +/- 0.33 l/min] cycled at a power output equal to 62-67% maximal O2 consumption for 2 h in a warm environment (33 degrees C dry bulb, 50% relative humidity, wind speed 2.5 m/s). During exercise, they randomly received no fluid (NF) or ingested a small (SF), moderate (MF), or large (LF) volume of fluid that replaced 20 +/- 1, 48 +/- 1, and 81 +/- 2%, respectively, of the fluid lost in sweat during exercise. The protocol resulted in graded magnitudes of dehydration as body weight declined 4.2 +/- 0.1, 3.4 +/- 0.1, 2.3 +/- 0.1, and 1.1 +/- 0.1%, respectively, during NF, SF, MF, and LF. After 2 h of exercise, esophageal temperature (Tes), HR, and SV were significantly different among the four trials (P < 0.05), with the exception of NF and SF. The magnitude of dehydration accrued after 2 h of exercise in the four trials was linearly related with the increase in Tes (r = 0.98, P < 0.02), the increase in HR (r = 0.99, P < 0.01), and the decline in SV (r = 0.99, P < 0.01). LF attenuated hyperthermia, apparently because of higher skin blood flow, inasmuch as forearm blood flow was 20–22% higher than during SF and NF at 105 min (P < 0.05). There were no differences in sweat rate among the four trials. In each subject, the increase in Tes from 20 to 120 min of exercise was highly correlated to the increase in serum osmolality (r = 0.81-0.98, P < 0.02-0.19) and the increase in serum sodium concentration (r = 0.87-0.99, P < 0.01-0.13) from 5 to 120 min of exercise. In summary, the magnitude of increase in core temperature and HR and the decline in SV are graded in proportion to the amount of dehydration accrued during exercise.

Vasodilation contributes to the rapid hyperemia with rhythmic contractions in humans

1998 ◽  
Vol 76 (4) ◽  
pp. 418-427 ◽  
Author(s):  
J K Shoemaker ◽  
M E Tschakovsky ◽  
R L Hughson
Keyword(s):  
Blood Flow ◽  
Forearm Blood Flow ◽  
Perfusion Pressure ◽  
Blood Velocity ◽  
Pulsed Doppler ◽  
Contraction Rate ◽  
Handgrip Exercise ◽  
Arterial Diameter ◽  
Exercise Tests ◽  
Rhythmic Contractions

The hypothesis that the rapid increases in blood flow at the exercise onsetare exclusively due to the mechanical effects of the muscle pump was tested in six volunteersduring dynamic handgrip exercise. While supine, each subject completed a series of eightdifferent exercise tests in which brachial artery blood pressure (BP) was altered by25–30 mmHg (1 mmHg = 133.3 Pa) by positioning the arm above or below the heart.Two different weights, corresponding to 4.9 and 9.7% of maximal voluntary isometriccontraction, were raised and lowered at two different contraction rate schedules (1s:1s and 2s:2swork–rest) each with a 50% duty cycle. Beat-by-beat measures of mean blood velocity (MBV)(pulsed Doppler) were obtained at rest and for 5 min following step increases in work ratewith emphasis on the first 24 s. MBV was increased 50–100% above rest following the firstcontraction in both arm positions (p < 0.05). The increase in MBV from rest was greaterin the below position compared with above, and this effect was observed following the first andsubsequent contractions (p < 0.05). However, the positional effect on the increase inMBV could not be explained entirely by the ~40% greater BP in this position. Also, the greaterworkload resulted in greater increases in MBV as early as the first contraction, compared withthe light workload (p < 0.05) despite similar reductions in forearm volume followingsingle contractions. MBV was greater with faster contraction rate tests by 8 s of exercise. Itwas concluded that microvascular vasodilation must act in concert with a reduction in venouspressure to increase forearm blood flow within the initial 2–4 s of exercise.Key words: Doppler, mean blood velocity, arterial diameter,handgrip exercise, perfusion pressure.

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