Balancing Blood Pressure Regulatory Mechanisms Pathway Suite Network

	The balance between the regulatory mechanisms of blood pressure increases and decreases assures the maintenance of physiologically adequate levels of arterial blood pressure. Various metabolic, signaling and regulatory pathways prompt and/or regulate vasoconstriction, as well as the reabsorption of water and sodium by the kidney, and their net result translates in an increase in arterial blood pressure. On the other hand, those pathways that prompt and/or regulate vasodilation, natriuresis and water excretion have the opposite effect, resulting in a decreased blood pressure. A system well known for its vasoconstrictor effect is the renin-angiotensin system which consists of the enzymatic cascade giving rise to the active angiotensin peptides derived from the precursor angiotensinogen,  angiotensin II signaling via receptor type 1 and events downstream of it, and signaling by the steroid hormone aldosterone. Counteracting its effects is the kallikrein-kinin system which consists of the enzymatic cascade producing the active kinins and their downstream signaling resulting in vasodilation and natriuresis. Joining in these effects, is the same angiotensin II peptide but signaling via receptor type 2. Several enzymes involved in the generation of active angiotensin peptides, also metabolize the active kinins to inactive metabolites. Implicated in the angiotensin and kinin  effects are several G protein alpha subunit types and the events downstream of them that include intracellular signaling by protein kinase C (PKC) and the ‘calcium signaling kit’ of calcium transport and associated calcium/calcium-mediated signaling and their manifold manifestations.
In the context of angiotensin II signaling via receptor type 1, the increase in intracellular calcium concentration is believed to result in the activation of calcium/calmodulin dependent kinase I and IV and activation of several transcription factors that will eventually prompt the expression of aldosterone synthase, therefore resulting in the biosynthesis of aldosterone and its subsequent signaling. Aldosterone signals via its receptor, a member of the  nuclear receptor family whose activation results in the expression of targets genes, members of which include genes with important regulatory roles in renal sodium reabsorption. In the context of kinin signaling, the increase in intracellular calcium concentration leads to the production of nitric oxide and prostaglandins with a net vasodilator and natriuretic effect. Angiotensin II signaling has opposing effects on the Erk1/2 MAPK intracellular cascade depending on whether the receptor is type 1 or type 2. Also of importance are the pathways that revolve around cholesterol  and its regulation – cholesterol is the lipid molecule that is the precursor of all steroid hormones, including aldosterone. Signaling by the Srebf transcription factors controls the expression of genes involved in cholesterol and fatty acid biosynthetic pathways. Several anti-hypertensive drug pathways are available: statin, that targets the enzyme of the rate-limiting step of cholesterol biosynthesis and losartan, that is an angiotensin Ii receptor type 1 specific antagonist. The suite network will be updated as more diagrams are released for pathways with a role in the regulation of blood pressure.

Click here to explore the Mechanisms Mediating and Pertinent to Increased Blood Pressure Pathway Suite.

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Click here to explore the Mechanisms Mediating and Pertinent to Both Increased and Decreased Blood Pressure Pathway Suite.

Mechanisms Mediating and Pertinent to Increased Blood Pressure Pathway Suite

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Mechanisms Mediating and Pertinent to Decreased Blood Pressure Pathway Suite

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Mechanisms Mediating and Pertinent to Both Increased and Decreased Blood Pressure Pathway Suite

Click here to examine the Calcium Homeostasis Pathway Suite

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