Inclusion Criteria1. Radiological evidence of cerebral small vessel disease defined as: MRI evidence of lacunar infarct(s) (≤ 1.5 cm maximum diameter) and/or confluent deep white matter leukoaraiosis (≥ grade 2 on Fazekas scale).
2. Clinical evidence of cerebral small vessel disease can be:
1. lacunar stroke syndrome with symptoms lasting >24 hours occurring at least 5 months previously; OR
2. transient ischemic attack (TIA) lasting < 24 hours with limb weakness, hemi-sensory loss or dysarthria at least 5 months previously AND with MR DWI performed acutely showing lacunar infarction, OR if MRI is not performed within ten days of TIA, a lacunar infarction in an anatomically appropriate position is demonstrated on a subsequent MRI.
3. Age ≥ 50 years.
4. Imaging of the carotid arteries with Doppler ultrasound, CT angiography, or MR angiography in the previous 12 months demonstrating < 70% stenosis in both internal carotid arteries.
Exclusion Criteria1. Known diagnosis of dementia
2. Pregnancy or nursing
3. Cortical infarction (>1.5 cm maximum diameter)
4. Systolic BP < 90 and/or diastolic BP < 50
5. eGFR < 30 ml/min/1,73m2
6. Severe hepatic impairment
7. History of Lactose intolerance
8. Concomitant use of PDE5 inhibitors e.g. sildenafil, tadalafil, vardenafil
9. Patients receiving nicorandil and nitrates e.g. isosorbide mononitrate, isosorbide dinitrate, glyceryl trinitrate
10. Body weight > 130kg
11. Uncontrolled cardiac failure
12. Persistent or paroxysmal atrial fibrillation
13. History of "sick sinus syndrome" or other supraventricular cardiac conduction conditions such as sinoatrial or atrioventricular block
14. Uncontrolled COPD
15. Stroke or TIA within the last 5 months.
16. MRI not tolerated or contraindicated: MRI exclusion criteria: Participant has a cardiac pacemaker; recent surgery; vascular clips; metal implants or joint replacements that are not compatible with MRI; have had metal fragments in their eyes; has ever worked on a lathe; has shrapnel from a war injury; possibility of pregnancy
17. Known monogenic causes of stroke i.e. CADASIL
18. The patient does not wish to know important results from MRI
19. Unable to provide informed consent
20. Not possible to localise a. cerebri media bilaterally on inclusion day with Transcranial Doppler