Sildenafil, widely recognised under brand names such as Viagra and Revatio, is a phosphodiesterase type 5 (PDE5) inhibitor licensed in the UK for erectile dysfunction and pulmonary arterial hypertension. A common question arises regarding its vascular effects: is sildenafil a vasoconstrictor? Understanding the drug's mechanism of action is essential for safe prescribing and patient counselling. Sildenafil works by inhibiting the PDE5 enzyme, which leads to increased levels of cyclic guanosine monophosphate (cGMP) in vascular smooth muscle. This article clarifies sildenafil's true cardiovascular effects, explores its clinical uses under NHS and NICE guidance, and outlines important safety considerations for UK healthcare professionals and patients.

What Is Sildenafil and How Does It Work?

Sildenafil is a medication belonging to a class of drugs known as phosphodiesterase type 5 (PDE5) inhibitors. Originally developed for cardiovascular conditions, it gained prominence following its approval for erectile dysfunction (ED) in 1998 and subsequently for pulmonary arterial hypertension (PAH). In the UK, sildenafil is available under various brand names, including Viagra for ED and Revatio for PAH, as well as generic formulations. Most sildenafil products require a prescription, though Viagra Connect (50 mg) is available from pharmacies without a prescription under pharmacist supervision.

The mechanism of action centres on the inhibition of the PDE5 enzyme, which is highly expressed in vascular smooth muscle cells of the corpus cavernosum in the penis and in pulmonary vasculature, but also present in other vascular beds. Under normal physiological conditions, sexual stimulation triggers the release of nitric oxide (NO) in penile tissue. Nitric oxide activates guanylate cyclase, leading to increased levels of cyclic guanosine monophosphate (cGMP). This second messenger causes smooth muscle relaxation and subsequent vasodilation, facilitating increased blood flow.

PDE5 normally breaks down cGMP, thereby limiting the duration and extent of vasodilation. By selectively inhibiting PDE5, sildenafil prolongs the action of cGMP, enhancing and sustaining smooth muscle relaxation. This results in improved blood flow to specific vascular beds. Importantly, sildenafil does not initiate an erection independently; it requires natural sexual stimulation to trigger the nitric oxide–cGMP pathway. The drug's selectivity for PDE5 over other phosphodiesterase isoforms contributes to its therapeutic profile, though cross-reactivity with PDE6 (found in the retina) may account for visual side effects.

Sildenafil is rapidly absorbed following oral administration, with peak plasma concentrations typically reached within 30 to 120 minutes. High-fat meals can delay absorption and reduce maximum concentration, so taking it on an empty stomach may be preferable if a rapid effect is desired. Its half-life is approximately 3 to 5 hours, and it is metabolised primarily by hepatic cytochrome P450 enzymes (CYP3A4 and CYP2C9).

Clinical Uses of Sildenafil in the UK

In the United Kingdom, sildenafil is licensed for two principal indications, each with distinct dosing regimens and formulations. The most widely recognised use is for erectile dysfunction in adult men. NICE guidance acknowledges ED as a condition that can significantly impact quality of life and psychological wellbeing. Sildenafil is typically prescribed at doses of 25 mg, 50 mg, or 100 mg, taken approximately one hour before anticipated sexual activity, with a maximum frequency of once daily. The starting dose is usually 50 mg, adjusted according to efficacy and tolerability. A lower starting dose of 25 mg should be considered in men aged 65 years or older, those with hepatic impairment, severe renal impairment, or patients taking potent CYP3A4 inhibitors. While sildenafil for ED is not routinely available on the NHS except in specific circumstances (e.g., diabetes, prostate cancer treatment, spinal cord injury), Viagra Connect (50 mg) can be purchased from pharmacies following assessment by a pharmacist.

The second licensed indication is for pulmonary arterial hypertension, a progressive condition characterised by elevated blood pressure in the pulmonary arteries. In PAH, sildenafil acts as a pulmonary vasodilator, reducing pulmonary vascular resistance and improving exercise capacity. For this indication, the medication is prescribed at lower, more frequent doses—typically 20 mg three times daily. Revatio is the brand name used for PAH treatment and is available on NHS prescription. In the UK, PAH treatment with sildenafil should be initiated and supervised by specialist Pulmonary Hypertension Centres under NHS England commissioning arrangements.

Beyond these licensed uses, there is ongoing research into other potential applications, including high-altitude pulmonary oedema and Raynaud's phenomenon. However, these remain off-label uses in the UK with limited evidence, and should only be considered under specialist advice. Clinicians should ensure patients understand the specific indication for which sildenafil has been prescribed and the importance of adhering to recommended dosing schedules.

Safety Considerations and Contraindications

Sildenafil is generally well tolerated, but like all medications, it carries potential risks and is contraindicated in certain patient groups. The most significant contraindications are concurrent use with nitrates or nitric oxide donors (such as glyceryl trinitrate, isosorbide mononitrate, or recreational drugs like amyl nitrite) and co-administration with guanylate cyclase stimulators such as riociguat. These combinations can cause severe, potentially life-threatening hypotension due to the additive vasodilatory effects. Patients must be explicitly counselled never to use sildenafil alongside these medications, and this information should be clearly documented in medical records.

Other important contraindications include:

• Cardiovascular risk: Sildenafil should be avoided in men for whom sexual activity is inadvisable due to cardiovascular status, and typically in those with myocardial infarction or stroke within the past 6 months, unstable angina, severe heart failure, or uncontrolled arrhythmias.

• Hypotension: Patients with resting blood pressure below 90/50 mmHg should avoid sildenafil.

• History of non-arteritic anterior ischaemic optic neuropathy (NAION): Previous NAION in one eye is a contraindication to PDE5 inhibitor use.

Sildenafil should be used with caution in patients with:

• Hepatic impairment: Consider a lower starting dose (25 mg) in moderate to severe impairment.

• Severe renal impairment: A lower starting dose (25 mg) may be appropriate.

• Hereditary retinal disorders: Use is not recommended in conditions such as retinitis pigmentosa.

Common adverse effects include headache, facial flushing, dyspepsia, nasal congestion, and visual disturbances (such as a blue tinge to vision or increased light sensitivity). These are generally mild and transient. Rare but serious adverse events include priapism (prolonged erection lasting more than four hours, requiring emergency treatment), sudden hearing loss, and NAION. Patients with pre-existing risk factors for priapism (e.g., sickle cell disease, leukaemia, anatomical penile deformity) should be counselled about this risk.

Drug interactions require careful management. Alpha-blockers can enhance hypotensive effects; patients should be stable on alpha-blocker therapy before starting sildenafil (at 25 mg), and temporal separation of doses should be considered. CYP3A4 inhibitors (e.g., ketoconazole, ritonavir, erythromycin) may increase sildenafil levels, necessitating dose adjustments. Grapefruit juice can also increase sildenafil levels and should be avoided.

Patients should be advised to seek immediate medical attention if they experience chest pain during sexual activity (and not to take nitrates if they have recently taken sildenafil), sudden vision or hearing loss, or an erection lasting more than four hours. Suspected adverse reactions should be reported via the MHRA Yellow Card Scheme (yellowcard.mhra.gov.uk or the Yellow Card app).

Is Sildenafil a Vasoconstrictor or Vasodilator?

To directly address the question: sildenafil is a vasodilator, not a vasoconstrictor. This distinction is fundamental to understanding both its therapeutic effects and safety profile. The drug's pharmacological action—inhibition of PDE5 and subsequent elevation of cGMP levels—leads to relaxation of vascular smooth muscle and dilation of blood vessels. This vasodilatory effect is the basis for its efficacy in both erectile dysfunction and pulmonary arterial hypertension.

In erectile dysfunction, sildenafil facilitates vasodilation of the penile arteries and corpus cavernosum, allowing increased blood flow necessary for achieving and maintaining an erection. In pulmonary arterial hypertension, it causes vasodilation of the pulmonary vasculature, reducing the elevated pressures characteristic of this condition and improving right ventricular function and exercise tolerance.

The systemic vasodilatory effects of sildenafil are generally modest in healthy individuals at therapeutic doses, as PDE5 is not uniformly distributed throughout all vascular beds. However, the drug does cause mild reductions in systemic blood pressure—typically a decrease of 8–10 mmHg in systolic pressure and 5–6 mmHg in diastolic pressure. This effect is usually well tolerated but becomes clinically significant when sildenafil is combined with other vasodilators, particularly nitrates or alpha-blockers, or in patients with volume depletion.

There is no evidence that sildenafil acts as a vasoconstrictor under normal circumstances. Confusion may arise from the fact that erectile function involves a complex interplay of vasodilation and restriction of venous outflow (veno-occlusion), but sildenafil's role is exclusively vasodilatory. The medication does not constrict blood vessels; rather, it enhances the body's natural vasodilatory mechanisms in response to appropriate stimuli.

Patients and healthcare professionals should understand that sildenafil's cardiovascular effects are those of a mild, selective vasodilator. This knowledge is essential for appropriate patient selection, recognising contraindications, and counselling patients about potential side effects such as headache and flushing, which are direct consequences of vasodilation.

Frequently Asked Questions