Increase in Prostaglandins during Converting Enzyme Inhibition

1980 ◽  
Vol 59 (s6) ◽  
pp. 133s-135s ◽  
Author(s):  
S. L. Swartz ◽  
G. H. Williams ◽  
N. K. Hollenberg ◽  
F. R. Crantz ◽  
L. Levine ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Plasma Concentration ◽  
Sodium Intake ◽  
Thromboxane A2 ◽  
Normal Male ◽  
Converting Enzyme ◽  
Low Sodium ◽  
Converting Enzyme Inhibition ◽  
Male Subjects ◽  
Hypotensive Response

1. Because changes in the plasma concentration of angiotensin II and bradykinin appear inadequate to account completely for the hypotensive response to captopril, we measured changes in plasma prostaglandins in response to increasing doses of captopril in nine supine normal male subjects studied on both a high (200 mol/l) and low (10 mol/l) sodium intake. 2. On both the high and low sodium diets, captopril induced significant (P<0.01) increments in the 13,14-dihydro-15-keto metabolite of the vasodilatory prostaglandin E2, which correlated significantly with the fall in blood pressure (P<0.0001). 3. No significant changes were noted in the plasma levels of 6-keto-prostaglandins F1α or thromboxane B2, the stable products of prostacyclin and thromboxane A2 respectively.

Effect of Salt Supplementation on Sympathetic Activity and Endothelial Function in Salt-Sensitive Type 2 Diabetes

2019 ◽  
Vol 105 (4) ◽  
pp. e1187-e1200 ◽  
Author(s):  
Sara Baqar ◽  
Yee Wen Kong ◽  
Angela X Chen ◽  
Christopher O’Callaghan ◽  
Richard J MacIsaac ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Endothelial Function ◽  
Augmentation Index ◽  
Sodium Intake ◽  
Blood Pressure Monitoring ◽  
Muscle Sympathetic Nerve Activity ◽  
Burst Frequency ◽  
Low Sodium

Abstract Context Lower sodium intake is paradoxically associated with higher mortality in type 2 diabetes (T2D). Objective To determine whether sympathetic nervous system (SNS) activation and endothelial dysfunction contribute to these observations, we examined the effect of salt supplementation on these systems in people with T2D with habitual low sodium. We hypothesized that salt supplementation would lower SNS activity and improve endothelial function compared to placebo. Design We conducted a randomized, double-blinded, placebo-controlled crossover trial. Setting The study took place in a tertiary referral diabetes outpatient clinic. Participants Twenty-two people with T2D with habitual low sodium intake (24-hour urine sodium <150 mmol/24h) were included. Intervention Salt supplementation (100 mmol NaCl/24h) or placebo for 3 weeks was administered. Main outcome measures The primary outcome of SNS activity and endothelial function was assessed as follows: Microneurography assessed muscle sympathetic nerve activity (MSNA), pulse amplitude tonometry assessed endothelial function via reactive hyperemic index (RHI), and arterial stiffness was assessed via augmentation index (AI). Secondary outcomes included cardiac baroreflex, serum aldosterone, ambulatory blood pressure monitoring (ABPM), heart rate variability (HRV), and salt sensitivity. Results Compared to placebo, salt supplementation increased MSNA (burst frequency P = .047, burst incidence P = .016); however, RHI (P = .24), AI (P = .201), ABPM (systolic P = .09, diastolic P = .14), and HRV were unaffected. Salt supplementation improved baroreflex (slope P = .026) and lowered aldosterone (P = .004), and in salt-resistant individuals there was a trend toward improved RHI (P = .07). Conclusions In people with T2D and low habitual sodium intake, salt supplementation increased SNS activity without altering endothelial function or blood pressure but improved baroreflex function, a predictor of cardiac mortality. Salt-resistant individuals trended toward improved endothelial function with salt supplementation.

Brain angiotensin receptors and sympathoadrenal regulation during insulin-induced hypoglycemia

2001 ◽  
Vol 280 (4) ◽  
pp. R1162-R1168 ◽  
Author(s):  
René H. Worck ◽  
Dennis Staahltoft ◽  
Thomas E. N. Jonassen ◽  
Erik Frandsen ◽  
Hans Ibsen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Enzyme Inhibition ◽  
Blood Pressure Response ◽  
Pressure Response ◽  
Angiotensin Receptors ◽  
Converting Enzyme ◽  
Reflex Regulation ◽  
Conscious Rats ◽  
Converting Enzyme Inhibition

Simultaneous blockade of systemic AT1 and AT2 receptors or converting enzyme inhibition (CEI) attenuates the hypoglycemia-induced reflex increase of epinephrine (Epi). To examine the role of brain AT1 and AT2 receptors in the reflex regulation of Epi release, we measured catecholamines, hemodynamics, and renin during insulin-induced hypoglycemia in conscious rats pretreated intracerebroventricularly with losartan, PD-123319, losartan and PD-123319, or vehicle. Epi and norepinephrine (NE) increased 60-and 3-fold, respectively. However, the gain of the reflex increase in plasma Epi (Δplasma Epi/Δplasma glucose) and the overall Epi and NE responses were similar in all groups. The ensuing blood pressure response was similar between groups, but the corresponding bradycardia was augmented after PD-123319 ( P < 0.05 vs. vehicle) or combined losartan and PD-123319 ( P < 0.01 vs. vehicle). The findings indicate 1) brain angiotensin receptors are not essential for the reflex regulation of Epi release during hypoglycemia and 2) the gain of baroreceptor-mediated bradycardia is increased by blockade of brain AT2 receptors in this model.

Captopril-induced hypotension is inhibited by the bradykinin blocker HOE-140 in Na(+)-depleted marmosets

1995 ◽  
Vol 269 (4) ◽  
pp. H1221-H1228
Author(s):  
M. J. Panzenbeck ◽  
C. L. Loughnan ◽  
J. B. Madwed ◽  
R. J. Winquist ◽  
S. E. Fogal
Keyword(s):  
Blood Pressure ◽  
Hypotensive Effect ◽  
Induced Hypotension ◽  
Low Sodium Diet ◽  
Low Sodium ◽  
Arterial Blood ◽  
Vehicle Treatment ◽  
Hoe 140 ◽  
B2 Receptors ◽  
Hypotensive Response

Inhibition of angiotensin-converting enzyme (ACE) inhibits formation of angiotensin II and, by inhibition of kinin metabolism, may also increase vascular bradykinin. The present experiments were done in sodium-depleted, conscious, unrestrained marmosets (n = 5-11) to examine the contribution of bradykinin to ACE inhibitor-induced hypotension. Aortic blood pressure and heart rate (HR) were monitored via telemetry. After sodium depletion (low-sodium diet and furosemide), captopril (1 mg/kg po) caused a significant (P < 0.05) decrease in mean arterial blood pressure (MABP) (-34 +/- 3 mmHg, maximally, from 79 +/- 2 mmHg) but no change in HR compared with vehicle treatment. The bradykinin receptor antagonist HOE-140 (1 mg/kg sc) significantly inhibited the hypotensive response to captopril and caused marked tachycardia (+133 +/- 14 beats/min from 214 +/- 8 beats/min). HOE-140 (1 mg/kg sc) followed by vehicle administration had no effect on MABP but increased HR similarly. The hypotensive response to captopril was inhibited by HOE-140 regardless of the order of administration or the route of captopril administration (by mouth vs. subcutaneously). The hypotensive response to a renin inhibitor, A-72517 (3 mg/kg sc), was not inhibited by prior HOE-140 administration despite a similar HOE-140-induced tachycardia. These data suggest that the hypotensive effect of captopril in sodium-depleted, conscious marmosets is dependent on functional bradykinin B2 receptors. Also, blockade of B2 receptors uncovers marked tachycardia in this model, suggesting a tonic effect of bradykinin on control of HR in marmosets.

Salt and cardiovascular disease: insufficient evidence to recommend low sodium intake

2020 ◽  
Vol 41 (35) ◽  
pp. 3363-3373 ◽  
Author(s):  
Martin O’Donnell ◽  
Andrew Mente ◽  
Michael H Alderman ◽  
Adrian J B Brady ◽  
Rafael Diaz ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Cardiovascular Events ◽  
Sodium Intake ◽  
Dietary Factors ◽  
Dietary Sodium ◽  
Current Evidence ◽  
Current Guideline ◽  
Current Recommendation ◽  
Low Sodium

Abstract Several blood pressure guidelines recommend low sodium intake (&lt;2.3 g/day, 100 mmol, 5.8 g/day of salt) for the entire population, on the premise that reductions in sodium intake, irrespective of the levels, will lower blood pressure, and, in turn, reduce cardiovascular disease occurrence. These guidelines have been developed without effective interventions to achieve sustained low sodium intake in free-living individuals, without a feasible method to estimate sodium intake reliably in individuals, and without high-quality evidence that low sodium intake reduces cardiovascular events (compared with moderate intake). In this review, we examine whether the recommendation for low sodium intake, reached by current guideline panels, is supported by robust evidence. Our review provides a counterpoint to the current recommendation for low sodium intake and suggests that a specific low sodium intake target (e.g. &lt;2.3 g/day) for individuals may be unfeasible, of uncertain effect on other dietary factors and of unproven effectiveness in reducing cardiovascular disease. We contend that current evidence, despite methodological limitations, suggests that most of the world’s population consume a moderate range of dietary sodium (2.3–4.6g/day; 1–2 teaspoons of salt) that is not associated with increased cardiovascular risk, and that the risk of cardiovascular disease increases when sodium intakes exceed 5 g/day. While current evidence has limitations, and there are differences of opinion in interpretation of existing evidence, it is reasonable, based upon observational studies, to suggest a population-level mean target of &lt;5 g/day in populations with mean sodium intake of &gt;5 g/day, while awaiting the results of large randomized controlled trials of sodium reduction on incidence of cardiovascular events and mortality.

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