Archives of Medical Research and Health Sciences  ( ISSN : 2994-6379 )

Research Article - Volume 5, Issue 2 (2023)

Antihypertensive Drugs and Brain Autoregulation: Chronicled Points of View and Pathophysiological Experiences

Hebert Allan1*, MacLean Green2, Hugeness Greiver2, Meyerowitz Katz1

1Department of Medicine, University of Ottawa, ON, Canada

2Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada

Correspondence to: Hebert Allan, Department of Medicine, University of Ottawa, ON, Canada. E-mail:

Received: January 19, 2023; Accepted: February 15, 2023; Published: February 23, 2023

Citation: Allan H, Green M, Greiver H, Katz M. Antihypertensive Drugs and Brain Autoregulation: Chronicled Points of View and Pathophysiological Experiences. Arch Med Res Health Sci. 2023;1(1):1-6.

Copyright: © 2023 Allan H. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Background: Cerebral Autoregulation (CA) comprises a complex instrument characterized by the capacity of the cerebral microcirculation to contract and widen in reaction to varieties in Blood Weight (BP), pointing to keeping Cerebral Blood Stream (CBF) consistent. Systemic blood vessel hypertension increases cerebrovascular resistance, which can contrarily impact this vasomotor reaction, moving the CA bend to the correct. In this way, a slight hypotension might compromise the CBF and cause harm to brain tissue.

Objective: From a brief verifiable viewpoint, the physiological instruments by which Antihypertensive (ASAH) contributes to keeping up the astuteness of cerebral CA will be checked.

Methods: The fabric for this audit was taken mostly from electronic diaries. To gather distributions, PubMed e Cochrane databases of efficient surveys were utilized.

Results: Ponders have appeared that the capacity of CA remains unaltered in hypertensive since ASAH is competent in advancing a variable readaptation of CA. This advantageous impact on CA has been confirmed over the long time through exploratory and clinical models and happens through diverse instruments of activity.

Conclusion: The human brain is one of the organs that most advantage from ASAH. Brief- or long-term BP control does not cause brain hypo perfusion and does not compromise CA.


Antihypertensive operators; Blood vessel hypertension; Blood cerebral stream; Cerebrovascular autoregulation; Cerebrovascular reactivity.


The method by which Cerebral Blood Stream (CBF) remains generally consistent in spite of changes in Cerebral Perfusion Weight (CPP) and which depends on the degree to which vascular smooth muscle cells are extended in reaction to changes in Blood Weight (BP) is known as Cerebral Autoregulation (CA) or autoregulatory weight [1]. The vascular changes actuated by Systemic Blood vessel Hypertension (SAH), such as the thickening of the smooth muscle layer and intimal hyperplasia, advance a lessening in luminal breadth and an increment in Cerebrovascular Resistance (CVR). This pathophysiological preparation compares to one of the components by which SAH can influence microvascular reactivity, moving the CA bend towards higher values of its lower restrain, which in certain circumstances favors an increment in oxygen extraction divisions and a decrease in CBF and can result in neuronal electrical and metabolic disappointment [2,3]. In any case, in hypertensive individuals, the coming of CBF is additionally impacted by the pharmacological impact of antihypertensive (ASAH) treatment on the Blood Vessels (BV) [4]. The impact of ASAH on CBF can happen in a way: (a) by implication, through BP control and inversion of versatile auxiliary changes within the BV divider; (b) coordinate, through the activity of pharmacological specialists on the BV [5]. From a brief verifiable point of view, the physiological components by which ASAH operators contribute to keeping up the astuteness of CA will be looked into.


Antihypertensive Drugs as Cerebral Blood Stream Controllers

About a century after William Harvey's disclosure and in the blink of an eye after Stephen Hales performed the primary known BP estimation in history, a youthful teacher of medication in Berlin, Samuel Schaarschmidt, who terminated rashly in 1747, distinguished and recommended how to treat a definite clinical condition as “spastic choking of the arteries”, what is presently called “essential” or “primary” hypertension. Be that as it may, the histological bases of Schaarschmidt's disclosure were as of now known indeed some time recently BP was measured in people, as Richard Shinning and George Johnson appeared that unremitting "Bright's infection" was characterized by hypertrophy and remodeling of the heart divider, courses, and arterioles [6].

This versatile reaction diminishes push on the blood vessel divider and ensures arterioles, capillaries, and venules from this increment in BP. Over time, extra changes happen, counting the amassing of stringy proteins, elastin, and collagen and the degeneration of smooth muscle cells [7,8]. Depending on the seriousness, these changes can impact a few hemodynamic factors, counting CA [9].

Since the considerations created by Lassen [10], it has been known that the lower restraint of CA weight is the esteemed past in which compensatory vasodilation becomes insufficient and CBF diminishes, causing neurological indications. In hypertensive people, this “lower” weight esteem is higher, due to an unremitting adjustment, which shifts weight to the correct within the CA bend, causing neurological side effects to seem prior [11]. Subsequently, with BP at indeed marginally higher levels, neurological indications seem to emerge in a few hypertensive people, making ASAH treatment challenging.

In expansion to the increment in transmural weight, a few intracellular signaling cascades enacted by the Renin Angiotensin Aldosterone Framework (RAAS) may moreover contribute to the blood vessel histological changes displayed in hypertensive patients [12,13]. The RAAS impacts the CA reaction through vasoconstriction auxiliary to the incitement of Angiotensin 1 (AT1) receptors of smooth muscle cells, shown within the cerebral microcirculation [14]. As a result, over numerous a long time, the potential helpful benefits have been assessed of Angiotensin-Converting Protein (Pro) inhibitors or AT1 Receptor Blockers (ARB) on CA (Figure 1).

Figure 1: AR visualized as a graph of the correlation between Cerebral Blood Flow (CBF) and Cerebral Perfusion Pressure (CPP). CBF remains stable between Lower Limit (LL) and Upper Limit (UL) (portion B, plateau), however, it undergoes passive modifications below the LL (part A) and above the UL (part C) according to the changes in the CPP. The limits vary (SD) between and within individuals depending on a variety of factors. The reflex response of cerebrovascular reactivity is also illustrated.

Angiotensin-Converting Protein Inhibitors and Angiotensin 1 Receptor Blockers

Captopril was one of the primary drugs to preserve CBF indeed when BP was diminished past the lower constraint of CA. Utilizing a test demonstration of suddenly hypertensive rats, Strandgaard et al. [15] assessed the intense cerebrovascular impact of medicine, connected intravenously or intraventricularly, and appeared that intravenous utilization decreased the lower and upper limits of CA by 20% mmHg -30% mmHg and 50 mmHg-60 mmHg, respectively. The creators proposed that this reaction was mediated by the RAAS of the endothelial surface, basically within the resistance vessels (where the ACE is found), instead of the brain RAAS per se, since the same comes about were not watched when the application was intraventricular.

Muller found that persistent antihypertensive treatment with Expert inhibitors moreover reestablished CA. The creators assessed the impacts of perindopril on cruel blood weight, CBF, and CA weight in rats with renovascular hypertension (actuated by clipping of the left renal course) and normotensive rats. Their test comprised regulating either ASAH or saline intraperitoneally to creatures in both bunches for 11 weeks. At the start of treatment, the hypertensive rats had Systolic Blood Weight (SBP) between 150 mmHg -250 mmHg and the lower restrain of their CA pressure was 150 mmHg. Unremitting treatment driven to a lessening of 36% (p<0.05) and 60 mmHg in SBP and lower CA level, separately, conceivably due to the inversion of versatile blood vessel changes, and did not compromise CBF [16].

The good thing about pharmacological intercession on the RAAS expanded past test models. Moriwaki considered the impacts of losartan on the CBF of hypertensive patients with a past history of ischemic stroke, utilizing walking BP estimations and Single Photon Outflow Computed Tomography (SPECT) [17,18]. At first, the measurements of losartan managed was 25 mg/day and titrations were performed with the point of keeping up BP160 mmHg [n=14]). In connection to pattern parameters, this final gathering of patients appeared a critical increment in CBFV (p<0.003) and a decrease in CVR (p<0.001) after 6 months of rigorous treatment, which was not watched within the other bunches, without any harm to their CA [19].

Not at all like those ponders that assessed the impacts of long-term treatment, in their clinical trial Zhang investigated whether ASAH might compromise CPP and energetic CA within the early stages of treatment [20]. For this, among other parameters, CBFV and BP were measured in patients with gentle (n=12) and direct (n=9) hypertension and in solid volunteers (n=9), both at the standard of the study and 1-2 weeks after organization of the losartan-hydrochlorothiazide combination. All the hypertensive within the test had been recently analyzed and was not however utilizing hypotensive drugs. Sometime recently treatment, CBFV was comparative between the three groups and remained so at the conclusion of the follow-up period, in spite of a noteworthy decrease in BP (143 ± 7/88 ± 4 to 126 ± 12/77 ± 6 mmHg vs. 163 ± 11/101 ± 9 to 134 ± 17/84 ± 9, separately, gentle vs. direct hypertensive bunches, p<0.05). In see of this, the creators proposed that this upkeep of CBFV, in spite of the critical lessening in BP, was due to a quick adjustment of the cerebral vasculature to secure the brain from hypo perfusion, indeed within the early stages of treatment.

However, the advantage of pharmacological intervention on BP, within the brief or long term, goes past the working and tweaking of the RAAS. SAH can too be effectively treated with a variety of other antihypertensive operators without hurting CBF [21].

Calcium Channel Blocker

Regarding calcium channel blockers (CCBs), previous studies have shown that CBF and CA also have different effects. Ikeda reported that hypertensive rats treated with barnidipine or amlodipine had better blood pressure control compared with untreated controls (184 ± 2 vs. 138 ± 1, p<0.01), with CA curves trending towards the lower end. (142 ± 4 vs. 142 ± 4 vs.). .91 ± 4, p < 0.01), long-term his CCB treatment had a beneficial effect on her CBF maintenance during hypotension when assessed under conditions of graded pressure control, and these indicated that he Because he uses CCB, he hypothesizes that it is a safe drug for SAB patients. Save the CA. However, similar results were not found by Höllerhage, who found that nimodipine, a first-generation CCB, impairs CA capacity in hypertension-induced rats. Among other reasons, this discrepancy may be due to the route and time of administration used and the pharmacological properties of the different CCB(s), which differently influence the CA control.

β -Adrenergic Receptor Blockers

β -adrenergic receptor blockers are inhibitors of renin secretion, the precursor of Angiotensin II (AT2), and presumably of RAAS activity. A study that investigated the interaction between treatment with these medications and the RAAS in hypertensive humans showed a reduction in urinary aldosterone levels by 35% (p<0.001) and plasma levels of renin and AT2 by 80% (p=0.002) and 44% (p<0.02), respectively, confirming the high positive correlation between renin and AT2 (R2=0.05, p<0.001) and, therefore, the potential effect of Beta-Blockers (BB) on RAAS inhibition. Thus, by contributing to the suppression of the known deleterious action of RAAS hormones on the arterial wall and CVR, providing adequate BP control, and minimizing transmural stress, BB can also participate in the control of the CA. However, BB do not seem to improve arterial structure. Chillon and Baumbach evaluated the effects of perindopril and propranolol on arterial remodeling in spontaneously hypertensive rats.


Diuretics have some vasodilating activity, either through their effect on the endothelium (release of Nitric Oxide [NO] and endothelium-derived relaxing factor) or on smooth muscle cells (opening of Ca2+ channels activated by K+ or by the desensitization of Ca2+ channels linked to the Rho-RhoA kinase pathway). Likewise, α-2 agonists and BB also promote peripheral vasodilation through a central sympathetic block of α-1 receptors, increased availability of NO, and/or intrinsic sympathomimetic activity.


Thus, these agents also reduce vascular resistance by their direct action, favoring blood flow, which is especially important in the case of parenchymal or perforating arterioles, as they are naturally high-resistance vessels due to their greater tonus myogenic. And if, on the one hand, in the chronic stages of SAH, cerebral arterioles hypertrophy, on the other hand, they become more distensible, in part due to an increase in the thickness of the internal elastic lamina, which results in greater attenuation and less transmission of pulse pressure, minimizing damage related to hyperdynamic [22].

This adaptive response is further potentiated with the use of ASAH. In a comparative study, the increase in carotid artery compliance was more pronounced with ACE inhibitors than with diuretics when blood pressure was similarly reduced, suggesting a direct effect of ACE inhibitors on arterial compliance. The same positive effects were also observed with CCB and ARB, especially due to their effects on arterial compliance. Therefore, as the remodeling concentric hypertrophy of parenchymal arterioles is alleviated, antihypertensive therapy and long-term blood pressure management help reduce CVR, and the lower limit of the CA curve again shifts to the left, increasing the margin of safety. It can lower blood pressure without compromising CBF.


The human brain is one of the organs that benefit most from ASAH. Short-term or long-term blood pressure control does not cause cerebral hypoperfusion, does not affect CA, and has beneficial effects on some structural and functional changes in the brain. The structure of cerebral arterioles was studied in untreated animals or animals treated with different doses of ACE inhibitors and/or the same dose of BB for 3 months. The authors used reduction in external artery diameter (EAD) as a remodeling marker and found that each dose of ACE inhibitor significantly attenuated the reduction in EAD, but not the use of BB. Since ACE inhibitors, unlike BB, inhibit bradykinin inactivation, we cannot exclude the possibility that this remodeling is associated not only with the blockade of AT2 function but also with increased bradykinin activity.


On behalf of all authors, the corresponding author declares that no conflict of interest exists.


The authors have not declared any specific grants for this research from funding agencies in the public, commercial, or non-profit sectors.


Not applicable.


 Not applicable.


1. Ahuja CS, Wilson JR, Nori S, Kotter MRN, Druschel C, Curt A, et al. Traumatic spinal cord injury. Nat Rev Dis Primers. 2017;3:17018.

2. Kovacic K, Li BUK. Cyclic vomiting syndrome: A narrative review and guide to management. Headache. 2021;61(2):231-243.

3. de Vries F, Lobatto DJ, Verstegen MJT, van Furth WR, Pereira AM, Biermasz NR. Postoperative diabetes insipidus: how to define and grade this complication?. Pituitary. 2021;24(2):284-291.

4. Fabbrocini G, Cantelli M, Masarà A, Annunziata MC, Marasca C, Cacciapuoti S. Female pattern hair loss: A clinical, pathophysiologic, and therapeutic review. Int J Womens Dermatol. 2018;4(4):203-211.

5. Martin KS, Azzolini M, Lira Ruas J. The kynurenine connection: how exercise shifts muscle tryptophan metabolism and affects energy homeostasis, the immune system, and the brain. Am J Physiol Cell Physiol. 2020;318(5):C818-C830.

6. Calviello LA, Donnelly J, Zeiler FA, Thelin EP, Smielewski P, Czosnyka M. Cerebral autoregulation monitoring in acute traumatic brain injury: what's the evidence?. Minerva Anestesiol. 2017;83(8):844-857.

7. Brady KM, Mytar JO, Kibler KK, Hogue CW Jr, Lee JK, Czosnyka M, et al. Noninvasive autoregulation monitoring with and without intracranial pressure in the naive piglet brain. Anesth Analg. 2010;111(1):191-195.

8. Longhi L, Gritti P, Ferri F, Lorini L, Lanterna A. Pressure Autoregulation Evaluated Measuring Brain Tissue Oxygen Tension in Patients With Moyamoya Syndrome. J Neurosurg Anesthesiol. 2021;33(2):183-184.

9. Ono N. Microcirculation in the brain: viewpoint of autoregulation. Nihon Yakurigaku Zasshi. 1999;113(4):203-210.

10. Segarra M, Aburto MR, Acker-Palmer A. Blood-Brain Barrier Dynamics to Maintain Brain Homeostasis. Trends Neurosci. 2021;44(5):393-405.

11. Riberholt CG, Olesen ND, Thing M, Juhl CB, Mehlsen J, Petersen TH. Impaired Cerebral Autoregulation during Head Up Tilt in Patients with Severe Brain Injury. PLoS One. 201611;11(5):e0154831.

12. Wettervik TS, Engquist H, Howells T, Lenell S, Rostami E, Hillered L, et al. Arterial Oxygenation in Traumatic Brain Injury-Relation to Cerebral Energy Metabolism, Autoregulation, and Clinical Outcome. J Intensive Care Med. 2021;36(9):1075-1083.

13. Donnelly J, Aries MJ, Czosnyka M. Further understanding of cerebral autoregulation at the bedside: possible implications for future therapy. Expert Rev Neurother. 2015;15(2):169-185.

14. Zweifel C, Dias C, Smielewski P, Czosnyka M. Continuous time-domain monitoring of cerebral autoregulation in neurocritical care. Med Eng Phys. 2014;36(5):638-645.

15. Tiba MH, McCracken BM, Leander DC, Colmenero Mahmood CI, Greer NL, Picton P, et al. Trans-Ocular Brain Impedance Indices Predict Pressure Reactivity Index Changes in a Porcine Model of Hypotension and Cerebral Autoregulation Perturbation. Neurocrit Care. 2022;36(1):139-147.

16. Xiong Y, Xiong Y, Zhu P, Wang Y, Yang H, Zhou R, et al. The Role of Gut Microbiota in Hypertension Pathogenesis and the Efficacy of Antihypertensive Drugs. Curr Hypertens Rep. 20216;23(8):40.

17. van Twist DJL, Kietselaer BLJH. Intravenous antihypertensive drugs: a double-edged sword?. J Hyperten. 2023;41(2):220-222.

18. Aronow WS. Treatment of resistant hypertension. Future Cardiol. 2020;16(5):353-356.

19. Refoios Camejo R, McGrath C, Herings R, Meerding WJ, Rutten F. Antihypertensive drugs: a perspective on pharmaceutical price erosion and its impact on cost-effectiveness. Value Health. 2012;15(2):381-388.

20. Parati G, Ravogli A, Mutti E, Santucci C, Omboni S, Mancia G. Ambulatory blood pressure monitoring in the evaluation of antihypertensive drugs. J Hypertens Suppl. 1994;12(8):S9-S15.

21. Zanchetti A. The antiatherogenic effects of antihypertensive drugs: experimental and clinical evidence. Clin Exp Hypertens A. 1992;14(1-2):307-331.

22. Kreutz R, Narkiewicz K, Kjeldsen S, Oparil S, Mancia G, Burnier M. Circadian variations in blood pressure and their implications for the administration of antihypertensive drugs: is dosing in the evening better than in the morning?. J Hypertens. 2020;38(8):1396-1406.