Arterial hypertension, a prevalent systemic condition, affects approximately 35% of the global population according to the World Health Organization [1]. Medications used for its management may induce hyposalivation and xerostomia [[2], [3], [4], [5], [6], [7], [8], [9]]. Hyposalivation, characterized by reduced salivary flow, is linked to various oral complications, including heightened tooth loss, dysgeusia, challenges in adapting to dentures, increased caries risk, and periodontal disease due to reduced immunoglobulin protection and self-cleaning. Moreover, hyposalivation is a recognized risk factor for halitosis and burning mouth [10,11], common complaints in patients on continuous medication for chronic systemic diseases [[12], [13], [14]].

Hyposalivation is generally defined as an unstimulated salivary flow rate below 0.1 ml/min or a stimulated flow rate below 0.5 ml/min [4]. Reduced salivary flow and increased saliva viscosity heighten susceptibility to dental caries, oral fungal infections, oral mucositis, swallowing difficulties, halitosis, and early tooth loss, all impacting the quality of life for patients with hypertension [3,6].

Saliva quality, influenced by factors such as protein content and inorganic components like calcium, is closely related to its viscosity [6]. Elevated concentrations of proteins and electrolytes significantly affect salivary properties and function [7].

The major salivary glands produce approximately 90% of salivary fluid, while the minor salivary glands contribute about 10%. Notably, minor salivary glands secrete a relatively significant fraction of salivary mucins, crucial for lubricating oral surfaces [10].

Saliva contains a higher proportion of water compared to plasma, approximately twice the amount. This disparity results in insufficient volume of water absorbed through osmosis [[16], [17], [18], [19], [20], [21], [22]]. The process of saliva production, including water extraction and related activities, demands substantial amounts of oxygen and essential elements, essential for the intense metabolic exchanges occurring within glandular cells. Actively functioning salivary glands consume five times more energy than when at rest, primarily sourced from adenosine triphosphate (ATP) molecules [23]. Salivary glands work against osmotic and pressure gradients, leading to an elevated ratio of CO2 to O2 and a higher number of catabolites [19].

Systemic diseases and daily medications can alter both saliva quantity and quality, significantly impacting a patient's overall quality of life [6]. Common antihypertensive drugs, such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, beta-blockers, calcium channel blockers, and diuretics, are widely used in managing hypertension [3].

Antihypertensive medications primarily target central alpha 2 adrenergic receptors within salivary glands, leading to reduced saliva production and often resulting in dry mouth [4]. β-adrenergic receptor agonists, like isoproterenol, induce salivary secretion with a higher protein concentration compared to angiotensin II receptor blockers. However, determining which antihypertensive medications have a higher propensity to induce xerostomia remains challenging due to limited evidence [4].

Classes of antihypertensive drugs, including alpha- and beta-adrenergic blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor antagonists, are also linked to salivary dysfunction. Alpha 1 antagonists (tyrosine and prazosin) and alpha 2 antagonists (clonidine) reduce salivary flow, while beta-blockers (atenolol and propranolol) decrease salivary protein levels [4,15,16]. Fig. 1 illustrates a diagram presenting the most frequently used antihypertensive drugs and their respective side effects.

Efficient methods for stimulating salivary flow, such as chewing, systemic sialogogues, local medication, electrical stimulation, acupuncture, and saliva substitutes, have limitations. The prevailing treatment approach often involves prolonged use of artificial saliva, although certain types may potentially affect tooth enamel integrity [13,[24], [25], [26], [27], [28]].

Photobiomodulation (PBM) is a potential treatment for hyposalivation, offering promising results and potential therapeutic value in managing this condition [19,[29], [30], [31], [32]]. PBM effectively modulates various biological responses, particularly in an inflammatory context, displaying anti-inflammatory effects by reducing inflammation and downregulating pro-inflammatory cytokines, thus promoting tissue healing and regeneration [35,36].

Light, a powerful modulator of biological processes, converts light energy into usable cellular energy, affecting cellular function through mechanisms like increased production of mitochondrial adenosine triphosphate (ATP), enhanced cellular glucose consumption, alterations in intracellular calcium levels, and increased mitochondrial count. These effects significantly influence cellular function, holding implications for diverse physiological processes [33,34]. Mitochondria, primarily targeted by light, house cytochrome C oxidase, acting as the photoreceptor and involving CuA and CuB sites in various cell types. This interaction partially explains the broad effects observed with PBM. The excitation of these photoreceptor molecules initiates a cascade of reactions termed cell signaling. Following the interaction with cytochrome C oxidase, nitric oxide dissociates from the enzyme's catalytic center, triggering downstream effects within cellular processes. This intricate mechanism emphasizes the complex interplay between light, cellular components, and signaling pathways in PBM [33,37]. Fig. 2 shows the main effects of PBM.

Scientific literature supports PBM's positive effects on salivary glands, showing increased ducts, epithelial cell mitosis, protein synthesis stimulation, and improved blood microcirculation. Furthermore, PBM enhances mitochondrial activity, resulting in increased ATP availability, enhanced cellular glucose consumption, and augmented cell proliferation [16,19,[38], [39], [40], [41]].

This study aims to investigate PBM's impact on salivary flow in individuals using antihypertensive medications. By exploring the effects of PBM on salivary glands, we seek to comprehend its potential in ameliorating hyposalivation and its relevance in clinical contexts. The primary hypothesis of this pilot clinical trial is that photobiomodulation can significantly increase the salivary production in patients with hyposalivation induced by anti-hypertensive drugs.