Is Cialis a Systemic Vasodilator?
Yes, tadalafil (Cialis) is a mild systemic vasodilator, though its vasodilatory effects are relatively modest compared to other vasodilators. 1
Mechanism of Vasodilation
Tadalafil functions as a systemic vasodilator through the following mechanism:
- It inhibits phosphodiesterase type-5 (PDE5), which normally breaks down cyclic guanosine monophosphate (cGMP) in vascular smooth muscle 2
- By preventing cGMP degradation, tadalafil enhances and prolongs the vasodilating effects of nitric oxide, leading to smooth muscle relaxation and vasodilation throughout the body 2
- This vasodilatory mechanism is not limited to penile tissue—PDE5 is widely distributed in the heart, smooth muscle, and blood vessels throughout the body 3
Clinical Evidence of Systemic Vasodilation
The FDA label explicitly characterizes tadalafil as having "mild systemic vasodilatory properties":
- In healthy subjects, tadalafil 20 mg produces a mean maximal decrease in supine blood pressure of 1.6/0.8 mm Hg compared to placebo 1
- When combined with antihypertensive medications, tadalafil produces additive blood pressure-lowering effects: 3/2 mm Hg with amlodipine, 6/4 mm Hg with bendrofluazide, 4/1 mm Hg with enalapril, and 5/3 mm Hg with metoprolol 1
- The American College of Cardiology and European Society of Cardiology both classify PDE5 inhibitors, including tadalafil, as vasodilators that cause pulmonary vasodilation and have been studied for pulmonary arterial hypertension 4
Critical Safety Implications of Systemic Vasodilation
The systemic vasodilatory properties create several important clinical considerations:
- Absolute contraindication with nitrates: The combination can cause dangerous, potentially fatal hypotension because both are vasodilators acting through the NO/cGMP pathway 1
- At least 48 hours must elapse after the last dose of tadalafil before nitrate administration can be considered in life-threatening situations, and only under close hemodynamic monitoring 1
- Caution with alpha-blockers: Both tadalafil and alpha-blockers are vasodilators with blood pressure-lowering effects, creating additive hypotensive risk when combined 1
- Patients with left ventricular outflow obstruction (aortic stenosis, hypertrophic cardiomyopathy) can be particularly sensitive to vasodilators including PDE5 inhibitors 1
- Patients with severely impaired autonomic control of blood pressure may be particularly sensitive to the vasodilatory actions 1
Therapeutic Applications Beyond Erectile Dysfunction
The systemic vasodilatory properties have led to therapeutic applications beyond ED:
- Tadalafil is FDA-approved for pulmonary arterial hypertension, where its vasodilatory effects on pulmonary vasculature improve exercise capacity and hemodynamics 4
- Studies suggest potential cardiovascular-protective effects through elevation of endothelial-derived nitric oxide, improved hemodynamic indexes, and beneficial effects in patients with coronary heart disease, hypertension, and heart failure 3
- Chronic tadalafil administration may improve endothelial function beyond its acute vasodilatory effects 5
Clinical Bottom Line
While tadalafil is indeed a systemic vasodilator, the key clinical point is that its vasodilatory effects are mild and generally well-tolerated in most patients 1. However, this mild systemic vasodilation becomes clinically significant and potentially dangerous when combined with other vasodilators (particularly nitrates and alpha-blockers) or in patients with specific cardiovascular conditions that make them sensitive to vasodilatory effects 1.