Increasing blood pressure affects one million people all over the world and comes to the top in the cause of death. blood pressure doubles the risk of heart disease, coronary disease, congestive heart disease, stroke, kidney failure, and peripheral artery disease. Though blood pressure lowering medication decrease risk.
Blood pressure increases with age and vary among populations and even in the same country. Systolic blood pressure increases with age >60 years and diastolic blood pressure is going to decrease after age 55. So, widening the pulse pressure. In the united-state increasing high blood pressure is due to obesity. The prevalence of blood pressure and stroke mortality is higher. Environmental and genetic factors may contribute to local and racial variations in hypertensive prevalence. Now, people are living in a more urbanized area so their lifestyle changes and leads to obesity. 60% of hypertensive are 20% overweight. High sodium intake and low calcium and potassium intake contribute to high blood pressure. Urinary sodium to potassium ratio is stronger correlate sodium and potassium intake. Alcohol, low physical activity, and psychological stress contribute to high blood pressure.
Genes of blood pressure
High blood pressure genes contribute to environmental factors and associated conditions like obesity, dyslipidemia, insulin resistance. Many studies showed significant heritability component to blood pressure. Gene that code for many enzymes such as renin-angiotensin-aldosterone system, atrial natriuretic, beta 2 adrenoreceptors, and alpha receptor. The familial component of hypertension is 30-40%.epigenetic modification of DNA without changing DNA sequence. Epigenetic dysregulation has emerged as a hallmark of complex disease. Ongoing study shows suggest there might a relation between target organ damage and vascular disease leads to hypertension. The specific gene variant is associating with renal damage may contribute hypertensive nephropathy also CHD, stroke. In the future, it is possible that DNA and epigastric analyses may predict individual risk and target organ damage and will respond with specific drugs.
Mechanism of blood pressure
First, we need to understand the roots of the regulation of normal and elevated hypertension. Cardiac output is consist of stroke volume and heart rate and stroke volume affiliated with myocardial contractility.
Sodium is an extra-cellular ion when it takes in excessive amounts leads to an increase in vascular volume and cardiac output may expand. However, vascular bad have the capacity to auto-regulate. Initially increase in blood pressure leads to vascular expansion, over time peripheral resistance increases so decrease cardiac output or return to normal. Another clear theory is salt activates the neural, paracrine, and endocrine systems. Arterial pressure is increase due to salt intake, urinary sodium increases to maintain sodium balance. This mechanism called “pressure – natriuresis”.also contributing factors are increasing mineralocorticoid hormone and ESRD is a classic example of volume-dependent hypertension.
Autonomic nervous system
Adrenergic systems regulate short term as well as long term (hormonal and volume) effects of blood pressure. These receptors are activating by guanosine nucleotide-binding regulatory protein (G proteins) and downgraded second messengers. Receptors of the adrenergic system have been differentiating into α1, α2, β1, β2 receptors. α1 receptor mainly located on postsynaptic smooth muscle and activated by norepinephrine. α 2 receptors lie on presynaptic nerve terminals and synthetized norepinephrine and act by negative feedback to inhibit further norepinephrine release.
In the kidney, if you stimulate α 1 receptors leads to increase sodium reabsorption by renal tubules so you need to inhibit α 1 receptor to control blood pressure or you stimulate α 2 receptors (α 2 agonists) .β 1 receptor acts on the heart and produces increase cardiac output by increasing heart rate and contractility. In addition, it releases renin from the kidney. β 2 receptor release epinephrine and relax smooth muscle resulted in vasodilatation.
Circulating catecholamine concentration may affect the number of receptors. If a high amount of catecholamine present in the blood leads to a decrease in adrenergic receptors in the tissue, so the best example is orthostatic hypotension in pheochromocytoma. Conversely, if a low amount of catecholamine leads to increase adrenergic receptors resulted in rebound hypertension due to sudden withdraw of α 2 agonist clonidine as an example.
Arterial baroreceptors located in the carotid body and aortic arch when blood pressure is going to increase it will start firing give information to the brain which resulted in decrease sympathetic flow, decrease heart rate, and blood pressure. However, its activity decline or adaptation occurs to high blood pressure this is a tough situation to deal with.
Obese individuals, hypertension related to increased sympathetic outflow so we may get success by inhibiting it.
Renin- angiotensin aldosterone– blood preesure
There is an interesting mechanism between renin, angiotensin, and aldosterone. This system contributes to regulating blood pressure mainly by vasoconstriction by angiotensin 2 and absorption of sodium by aldosterone. Renin primary secret by 1. The decrease sodium level in ascending convoluted tubules correspond to macula densa cell 2. Decrease pressure in the afferent artery in kidney 3. Stimulation by β 1 receptors. Conversely, renin decrease by all three factors and also inhibited by angiotensin 2.
When renin is secreted into the circulation it degrades angiotensinogen to angiotensin 1 which is inactive molecules. To activate these molecules need ACE kininase 2 enzyme turn into activated angiotensin 2 which acts on AT 1 receptor. It also stimulates aldosterone in the adrenal gland from zona glomerulosa.
Renin secreting tumors are the best example of renin hypertension. Such as renal carcinoma, Wilms tumor, obstruction of the renal artery. Over time, it may damage by renin and might become less renin responsive.
Excess tissue angiotensin 2 may contribute to atherosclerosis, cardiac hypertrophy, and renal failure therefore we can target by pharmacologic therapy to prevent further damage.
Angiotensin 2 is the main factor for aldosterone secretion and may need a normal potassium level to its secretion. Aldosterone is a mineralocorticoid that increases sodium by amiloride-sensitive epithelial sodium channel so it exchanging sodium for potassium.
Mineralocorticoid receptors are present in many organs, activation of these receptors leading to myocardial fibrosis, nephrosclerosis, vascular inflammation, and remodeling, it might be due to oxidative stress. This effect is worsened if large salt added into the body.to prevent these complications we can start a low dose of spironolactone (aldosterone antagonist)
Resistance to flow varies inversely with the forth power of the radius, so a small decrease in lumen size significantly increases resistance. In hypertensive individuals vessel remodeling refers to geometric alteration due to deposition of intracellular matrix and hypertrophy of cell leads to narrowing of the vessels. Apoptosis, low-grade inflammation, and vascular fibrosis also promote remodeling.
Arterial stiffness stiffened vessels less able to buffer short term alteration of flow. The index of arterial stiffness is determined by pulse wave velocity between carotid and femoral. Due to arterial stiffness, central aortic pressure may not correspond to brachial pressure. Increased arterial stiffness results in increase pulse wave velocity of the reflected wave. Due to this wave augmentation of aortic systolic blood pressure and decrease diastolic blood pressure. Mean arterial pressure is determined by cardiac output and peripheral resistance. The aortic augmentation index of arterial stiffness is calculated as the ratio of central arterial pressure to pulse pressure. And is independent predictors of cardiovascular disease and all-cause mortality.
Iron transport chain may have role hypertension, it was seen that it effect on vascular tone and intracellular ph. it increases the sodium entry lead to increase vascular tone by activating sodium-calcium exchange thereby increased calcium intracellularly. Increase ph sensitized calcium to contract smooth muscle.
Vascular endothelial also regulate vascular tone. It synthesized and secret vasoactive substances such as nitric oxide, a potent vasodilator. In hypertensive individuals, this mechanism is impaired so endothelin antagonists may lower blood pressure in resistant hypertension.
Limited study suggests that aerobic exercise, weight loss, and antihypertensive agents may improve vascular compliance and endothelium-dependent vasodilatation.
Immune mechanism inflammation and oxidative stress on blood pressure
Both hypertension and stiffness are associated with activation of innate and adaptive immunity inflammation and exudative injury is interrelated. It generates reactive oxygen species that modify T cell function and further enhance inflammation. In the kidney, this T cell infiltrates and disturbs pressure natriuresis leads to hypertension.
You can also watch my blog on obesity.
Thank you for your valuable time to read
Dr Manish Khokhar