Intravenous Pinacidil in the Acute Treatment of Hypertension

To study the systemic and regional hemodynamic effects of the new antihypertensive agent pinacidil, the authors administered intravenously two doses of pinacidil (0.1 mg/kg) to patients with hypertension after 3 days of randomized, double-blind pretreatment with either propranolol or placebo. Pinacidil administration decreased systemic arterial pressure and total peripheral vascular resistance in both groups of patients. It also decreased pulmonary artery wedge pressure, and increased cardiac output, heart rate, and plasma norepinephrine levels; the changes in cardiac output and heart rate were attenuated by propranolol pretreatment. In addition, propranolol-pretreated patients responded to pinacidil with a decrease in forearm blood flow. In contrast, pinacidil administration exerted no significant effects on right atrial pressure, stroke volume, or mean pulmonary arterial pressure alone or in combination with propranolol. The results show that pinacidil is a potent arterial dilator but has little effect on the venomotor tone in patients with hypertension.

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Acute Hemodynamic Effects of Pinacidil in Hypertensive Patients with and without Propranolol Pretreatment

Stone

Wellington

Willick

et al. 1991

The Journal of Clinical Pharma

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Effect of pinacidil on renal haemodynamics, tubular function and plasma levels of angiotensin II, aldosterone and atrial natriuretic peptide in healthy man

Nielsen

Pedersen

1993

Eur J Clin Pharmacol

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The effects of pinacidil on renal haemodynamics, tubular function evaluated by the lithium clearance technique and the plasma levels of angiotensin II (Ang II), aldosterone (Aldo) and atrial natriuretic peptide (ANP) have been evaluated in 12 healthy volunteers given pinacidil 0.1 mg/kg IV in comparison with a placebo given to 13 different healthy volunteers. Pinacidil induced significant reductions in glomerular filtration rate (-5%), renal plasma flow (-12%), urine output (-35%), urinary sodium excretion (-20%), and the fractional excretion of sodium (-17%) and potassium (-29%). Lithium clearance and proximal and distal absolute and fractional reabsorption of sodium were not significantly changed. Ang II and Aldo were significantly increased (80% and 115%, respectively) and ANP was unchanged. The mean arterial blood pressure was not significantly changed by pinacidil, but the heart rate was increased (22%). It is concluded that bolus IV injection of pinacidil in healthy subjects reduced renal blood flow, urine volume and the urinary excretion of sodium and potassium, whereas segmental tubular function was unchanged. The increase in heart rate and activation of the renin-angiotensin-aldosterone system are most likely to be secondary to stimulation of the sympathetic nervous system caused by the vasodilator effect of pinacidil.

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Pinacidil Pretreatment Improves Vascular Reactivity After Shock Through PKCα and PKC[Latin Small Letter Open E] in Rats

Li²,

Yang³

et al. 2012

Journal of Cardiovascular Pharmacology

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We investigated the beneficial effect of pinacidil pretreatment on vascular reactivity, calcium sensitivity, and animal survival after hemorrhagic shock, its relationship to protein kinase Cα (PKCα), protein kinase Cε (PKCε), and adenosine. Using hemorrhagic shock rats, the protective effects of different extents of pinacidil pretreatment on vascular reactivity and in which the roles of PKCα, PKCε, and adenosine were observed. Pinacidil pretreatment significantly improved shock-induced decrease of vascular reactivity of superior mesenteric artery, which was antagonized by the PKCα antagonist Gö-6976 (5 × 10 mole/L) and PKCε pseudosubstrate inhibitory peptide (1 × 10 mole/L). Pinacidil pretreatment induced the translocation of PKCα and PKCε from the cytoplasm to the membrane. This translocation of PKCα and PKCε was eliminated by adenosine A1 receptor antagonist DPCPX (1 × 10 mole/L). As compared with simple fluid resuscitation, combination with pinacidil pretreatment significantly improved the vascular reactivity and survival rate of hemorrhagic-shocked rats. These results suggested that pinacidil pretreatment could induce good protective effects on vascular reactivity and calcium sensitivity after hemorrhagic shock mainly through the activation of PKCα and PKCε via adenosine A1 receptor, and this protective effect made an important contribution to the overall outcome of shock therapy.

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Intravenous Pinacidil in the Acute Treatment of Hypertension

Cited by 3 publications

References 19 publications

Acute Hemodynamic Effects of Pinacidil in Hypertensive Patients with and without Propranolol Pretreatment

Acute Hemodynamic Effects of Pinacidil in Hypertensive Patients with and without Propranolol Pretreatment

Effect of pinacidil on renal haemodynamics, tubular function and plasma levels of angiotensin II, aldosterone and atrial natriuretic peptide in healthy man

Pinacidil Pretreatment Improves Vascular Reactivity After Shock Through PKCα and PKC[Latin Small Letter Open E] in Rats

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