Effects of cardiotropic drugs on vascular stiffness and diastolic pressure ratio

Abstract

Research on the relation between diastolic blood pressure (DBP) and pulse wave velocity (PWV) is essential, especially for comprehending cardiovascular risk and the outcomes of various pharmacological interventions. PWV is a widely recognized measure of arterial stiffness, while DBP mainly depends on the artery state. The effect of cardiovascular drugs (CVDs) on these parameters remains inadequately defined, particularly regarding their influence on the DBP to PWV ratio (DBP/PWV). This specific interaction has garnered increasing attention within the field of cardiovascular research. In clinical settings, the DBP/PWV ratio is sometimes used to evaluate the impact of drugs (e.g., antihypertensives, statins, and antidiabetic agents) on arterial stiffness relative to blood pressure control. Each drug acts differently on blood vessels, heart rate, and vascular tone, thus influencing DBP and PWV. The specific investigation of the DBP/PWV ratio in animal models, including pigs, is somewhat limited. In addition, while some essential oils, such as E. ciliata (ECEO), have been reported to have antiarrhythmic [1] and hypotensive or vasodilatory effects [2], till now there has been no research linking the essential oils' action to the modulation of arterial stiffness and DBP/PWV ratio. In this study, using anesthetized in vivo pigs we aimed to assess the effects of ECEO, compare its effectiveness with various CVDs on the DBP/PWV ratio, and reveal their mechanisms of action. We measured systolic and diastolic blood pressure (SBD and DBP, respectively) and heart rate via invasive catheterization of the carotid artery. The blood pressure waveform and femoral artery pulse were recorded for 30 min and were used to calculate PWV. We assessed the effects of various drugs on heart rate and blood pressure, and calculated pulse wave speed and its relationship to DBP. Our results demonstrate that in the pig model, essential oils like ECEO have been reported to modulate heart rate and reduce blood pressure [2] and may influence DBP through the relaxation of blood vessels. The drug tends to reduce PWV from 10.5 to a minimal value of 4.1 m/s, and after 30 min reached a new level at 8.9 m/s. If ECEO reduces arterial stiffness and DBP, it might theoretically modulate the DBP/PWV ratio, but this remains unclear and is purely speculative without clinical evidence. Herbal essential oils have not been used or studied for measuring or modulating the DBP/PWV ratio in any significant way in scientific research. They are primarily used for their general health benefits. In this study, for the first time, we addressed arterial stiffness or cardiovascular markers like PWV using ECEO. Furthermore, the modulating effect of other CVDs, such as salbutamol and dobutamine (beta-adrenergic agonists), glycerol trinitrate (nitric oxide donor), diltiazem (calcium channel blocker), and lidocaine (sodium channel blocker), was assessed and compared. We demonstrate that lidocaine, diltiazem, and glycerol trinitrate, like with the ECEO, modified DBP/PWV linear ratio to 5-8 (mmHg / m/s) (Fig. 1). In contrast, using beta-adrenergic agonists (e.g., salbutamol and dobutamine), the calculated slope of DBP/PWV ratio was of bigger value. This might indicate that beta-adrenergic agonists alter blood pressure through mechanisms beyond vascular stiffness alone. While our data demonstrate that CVDs can influence DBP and PWV, the precise mechanisms by which these drugs differentially affect DBP versus PWV are still unclear. More research is needed to understand drug class-specific effects on the DBP/PWV ratio, dose-dependent effects, their impact on the ratio over time, and/or interaction between drugs since many patients are treated with multiple CVDs simultaneously. In addition, direct measurements of how different CVDs influence DBP and PWV in pig models under various physiological and pathological conditions (e.g., induced hypertension or heart failure) are needed. These models could provide insights into the dynamic changes in arterial stiffness and blood pressure regulation.