Renovascular Hypertension Medication

All classes of antihypertensive medications are used to treat RVHT; however, the most effective therapy is with an ACE inhibitor, which minimizes the ischemia-induced rise in angiotensin production. Because hypertension may be dependent on angiotensin II, antihypertensives that inhibit renin or angiotensin II are used widely. An ACE inhibitor markedly decreases blood flow through the stenotic kidney; thus, in patients with a solitary kidney or bilateral renovascular disease, blood pressure may fall rapidly, with an ensuing deterioration in renal function. This usually is reversible upon discontinuation of the medication.

Although less clinical experience exists with newer angiotensin receptor blockers (ARBs), they appear to be as effective as ACE inhibitors in experimental models. In patients without hemodynamically significant renal artery disease, an increase in serum creatinine level of up to 35% above baseline with an ACE or ARB is considered acceptable and is not a reason to withhold treatment unless hyperkalemia develops. Both beta-blockers and diuretics also are used, the latter often in conjunction with ACE inhibitors. Diuretics enhance sodium and water diuresis, thereby eliminating the volume-mediated component of RVHT. Calcium channel blockers (CCBs) may provide equally good control of hypertension, with presumably less impairment in function of the ischemic kidney than ACE inhibitors.

A selective aldosterone inhibitor, eplerenone (INSPRA) is now available for the treatment of hypertension. It selectively blocks aldosterone at the mineralocorticoid receptors in epithelial (eg, kidney) and nonepithelial (eg, heart, blood vessels, brain) tissues, thus decreasing blood pressure and sodium reabsorption. The adult dose is 50 mg PO qd and it may be increased after 4 wk, not to exceed 100 mg/d. Contraindications include documented hypersensitivity, hyperkalemia, coadministration with drugs causing increased potassium, type 2 diabetes with microalbuminuria, and moderate-to-severe renal insufficiency (ie, CrCl < 50 mL/min or serum creatinine >2 mg/dL [males] or >1.8 mg/dL [females]). Eplerenone is a CYP450 3A4 substrate, thus potent CYP3A4 inhibitors (eg, ketoconazole) increase serum levels about 5-fold, whereas less potent CYP3A4 inhibitors (eg, erythromycin, saquinavir, verapamil, fluconazole) increase serum levels about 2-fold. Grapefruit juice increases serum levels about 25%.

Coadministration with potassium supplements, salt substitutes, or drugs known to increase serum potassium (eg, amiloride, spironolactone, triamterene, ACE inhibitors, angiotensin II inhibitors) increases risk of hyperkalemia. Eplerenone may cause hyperkalemia, headache, or dizziness. Caution is advised with hepatic insufficiency.

Class Summary

These agents minimize an ischemia-induced rise in angiotensin production. Because hypertension may be dependent on angiotensin II, antihypertensives that inhibit renin or angiotensin II are used widely. All drugs in this class have similar action and adverse effects.

Captopril (Capoten)

Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion. Excreted primarily by the kidney.

Enalapril (Vasotec)

Competitive inhibitor of ACE. Reduces angiotensin II levels and decreases aldosterone secretion.

Lisinopril (Zestril, Prinivil)

Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion.

Class Summary

Angiotensin II is the primary vasoactive hormone of the renin-angiotensin system and plays an important role in the pathophysiology of hypertension. Besides being a potent vasoconstrictor, angiotensin II stimulates aldosterone secretion by the adrenal gland; thus, ARBs decrease systemic vascular resistance without a marked change in heart rate by blocking the effects of angiotensin II. Type 1 angiotensin receptors are found in many tissues, including vascular smooth muscle and the adrenal gland. Type II angiotensin receptors also are found in many tissues, although their relationship to cardiovascular hemostasis is not known. The affinity of ARBs is approximately 1000-fold greater for the type I angiotensin receptor than for the type II angiotensin receptor.

In general, ARBs do not inhibit ACE, other hormone receptors, or ion channels. ARBs interfere with the binding of formed angiotensin II to its endogenous receptor. Experience in the treatment of RVHT with this group of drugs still is limited. Losartan and valsartan are specific and selective nonpeptide angiotensin II receptor antagonists that block the vasoconstricting and aldosterone-secreting effects of angiotensin II.

Other ARBs have been approved by the FDA, including olmesartan (Benicar). Olmesartan is initiated at 20 mg PO qd and may be increased to 40 mg/d after 2 wk if further BP reduction is required.

Losartan (Cozaar)

For patients unable to tolerate ACE inhibitors. May induce a more complete inhibition of the renin-angiotensin system than ACE inhibitors, does not affect response to bradykinin, and is less likely to be associated with cough and angioedema. Compared to the ACE inhibitors (eg, captopril, enalapril), losartan is associated with lower incidence of drug-induced cough, rash, and taste disturbances.

Valsartan (Diovan)

For patients unable to tolerate ACE inhibitors. May induce more complete inhibition of renin-angiotensin system than ACE inhibitors. Does not affect response to bradykinin and is less likely to be associated with cough and angioedema. Compared with ACE inhibitors (eg, captopril, enalapril), it is associated with lower incidence of drug-induced cough, rash, and taste disturbances.

Class Summary

Compete with adrenergic neurotransmitters (eg, catecholamines) for binding at sympathetic receptor sites. Atenolol and metoprolol, in low doses, selectively block beta1-adrenergic receptors in the heart and vascular smooth muscle. Pharmacodynamic consequences of beta1-receptor blockade include a decrease in both resting and exercise heart rate and cardiac output and a decrease in both systolic and diastolic blood pressure. As with all selective adrenergic antagonists, selectivity for the beta1-receptor is lost at higher doses, and they can competitively block beta2-adrenergic receptors in the bronchial and vascular smooth muscles, potentially causing bronchospasm.

Actions that generally make beta-blockers useful in treating hypertension include a negative chronotropic effect that decreases the heart rate at rest and after exercise, a negative inotropic effect that decreases cardiac output, a reduction of sympathetic outflow from the CNS, and suppression of renin release from the kidneys. Thus, beta-blockers affect blood pressure via multiple mechanisms.

Metoprolol (Lopressor)

Selective beta1-adrenergic receptor blocker that decreases automaticity of contractions. During IV administration, carefully monitor blood pressure, heart rate, and ECG.

Atenolol (Tenormin)

Selectively blocks beta1-receptors with little or no effect on beta2 types.

Propranolol (Inderal, Betachron)

Although beta1 selective beta-blockers (eg, metoprolol) are preferred over nonselective agents in patients with asthma or pulmonary conditions in which acute bronchospasm would put them at risk (eg, COPD, emphysema, or bronchitis), all beta-blockers should be used with caution in these patients, particularly with high-dose therapy. Has membrane-stabilizing activity and decreases automaticity of contractions. Not suitable for emergency treatment of hypertension. Do not administer IV in hypertensive emergencies.

Class Summary

These agents provide control of hypertension associated with less impairment of function of the ischemic kidney. Suggested that they may have beneficial long-term effects, but this remains uncertain.

Diltiazem (Cardizem CD, Dilacor)

CCBs inhibit influx of extracellular calcium across both myocardial and vascular smooth muscle cell membranes. Serum calcium levels remain unchanged.

Resultant decrease in intracellular calcium inhibits contractile processes of myocardial smooth muscle cells, resulting in dilation of coronary and systemic arteries and improved oxygen delivery to myocardial tissue. In addition, total peripheral resistance, systemic blood pressure, and afterload are decreased.

Similar to verapamil in that it inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes.

Verapamil (Calan)

During depolarization, inhibits calcium ion from entering slow channels or voltage-sensitive areas of the vascular smooth muscle and myocardium.

Nifedipine (Adalat, Procardia)

Relaxes coronary smooth muscle and produces coronary vasodilation, which, in turn, improves myocardial oxygen delivery. Sublingual administration generally is safe, despite theoretical concerns.

Class Summary

Used only as an adjunct to other medications for RVHT, especially during acute hypertensive crisis. Furosemide is especially effective in managing pulmonary edema associated with hypertensive crises and may be particularly useful in patients unresponsive to other diuretics or those who have severe renal impairment.

Furosemide (Lasix)

Primarily appears to inhibit reabsorption of sodium and chloride in the ascending limb of the loop of Henle. These effects increase urinary excretion of sodium, chloride, and water, resulting in profound diuresis.

Renal vasodilation occurs following administration of furosemide. Renal vascular resistance decreases and renal blood flow is enhanced.

Hydrochlorothiazide (Esidrix, Microzide, HydroDIURIL)

Inhibits reabsorption of sodium in distal tubules, causing increased excretion of sodium and water and potassium and hydrogen ions.

Bumetanide (Bumex)

Increases excretion of water by interfering with chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in ascending loop of Henle. Does not appear to act in the distal renal tubule.

Class Summary

These agents are effective in reducing hypertension.

Nitroprusside (Nitropress)

Mainly used when patient presents with a hypertensive emergency secondary to RVHT. See Hypertension and Hypertensive Emergencies.

Class Summary

Newest class of antihypertensive drugs. Acts by disrupting the renin-angiotensin-aldosterone system feedback loop.

Aliskiren (Tekturna)

Direct renin inhibitor. Decreases plasma renin activity and inhibits conversion of angiotensinogen to angiotensin I (as a result, also decreasing angiotensin II) and, thereby, disrupts the renin-angiotensin-aldosterone system (RAAS) feedback loop. Indicated for hypertension as monotherapy or in combination with other antihypertensive drugs.