Laragh's lessons in pathophysiology and clinical pearls for treating hypertension

In previous lessons, I dealt with how to mechanistically diagnose to thereby treat individual ambulatory hypertensive patients by first performing a plasma renin test to identify whether the patient has primary sodium volume-mediated V hypertension (plasma renin activity [PRA] values <0.65 ng/mL/h) or a primary renin-mediated R hypertension (PRA >0.65 ng/mL/h). This method enables selection of the correct primary V or R type drug therapy and then, if necessary, guides the choice of appropriate secondary R or V drugs to control the hypertension. As discussed in previous lessons (XIV to XVIII), this method finds the best fit drug class using an objective, mechanistically based drug treatment strategy. It usually uses fewer drugs to more successfully treat the full range of ambulatory hypertensive disorders. An important prerequisite for using this new treatment method is an understanding of the Laragh volume vasoconstriction analytical model. By using the plasma renin test, it assesses the strength of one of the two final determinants of all blood pressure (BP) measurements, either normotension or hypertension. These are 1) the sodium volume factor, and 2) the plasma renin-angiotensin level. These two final determinants function in the framework of the Poiseuille equation. The equation states that the BP level is determined minute by minute by the cardiac output multiplied by the degree of arteriolar narrowing (the peripheral resistance). These two values are largely determined by the body sodium content that creates the volume factor and by the plasma renin that creates the angiotensin level, which continuously sets arteriolar tone. Because the cardiac output is determined primarily by the volume of the venous return delivered to the heart, the cardiac output is largely a function of the amount of sodium, and thus water, present in both the plasma and in the Donnan-connected extracellular fluids, which determine in turn, the volume of the venous return that determines the cardiac output. (A nice illustration of how this works is the finding that simply feeding extra salt promptly increases the cardiac output to produce physiologic left ventricular hypertrophy in normal or hypertensive people studied by echocardiogram; see Lesson XIV). Thus, arterial BP is a function of 1) the body sodium volume content (the cardiac output) and 2) the arteriolar peripheral resistance, set minute to minute by the plasma renin-angiotensin-mediated arteriolar vasoconstriction. A number of transient, regional inputs might modify the strength of either the sodium volume or the vasoconstrictor factor in the BP equation. These inputs include vasopressin, prostaglandins, and nitric oxide (NO) release. However, generally these influences are transient and regional, and are promptly buffered by constantly fine-tuning adjustments in the renin system servocontrol to regulate overall systemic arterial BP, and body sodium content. To summarize this approach, using plasma renin testing with our volume/vasoconstriction model (Lessons XIV and XV) the data show that there are basically two types of hypertension, either sodium-volume, V-mediated, or plasma renin-angiotensin, R-mediated. A sodium-volume excess is normally associated with suppressed plasma levels and, pathologically, with sodium-mediated low renin V hypertension (PRA values <0.65 ng/mL/h) and therefore, can be corrected by sodium depletion or a sodium volume-depleting V drug. Conversely, renin-mediated hypertensions are related to the level of plasma renin (>0.65 ng/mL/h) and corrected by an antirenin R drug. In this context, the ambulatory plasma renin value reliably indicates whether a hypertensive condition is largely sodium-mediated (PRA <0.65 ng/mL/h) or largely renin-mediated (PRA >0.65 ng/mL/h) and, when renin levels are close to 0.65 ng/mL/h, the transition point, it reflects a more subtle inappropriate excess of one or both of the two determinants. To use the volume/vasoconstriction model to guide the correct drug selection, two tenets need to be recognized to analyze and treat the BP of individual patients. The first tenet, just discussed, is that there are basically two types of hypertension—V or R mediated (see previous paragraph). The second and companion tenet is that there are also two different types of the V drugs that body sodium content and the R drugs that plasma renin this framework there are different types of R drugs of 1) renin using or 2) plasma angiotensin by in the and function an the or the of angiotensin to that also and are to the plasma and related extracellular the renin system These are the It be that of these antirenin system drug are of the renin with a different to be for the renin thereby BP, for when increases in renin are either by or In this the of renin system can be by increases in renin to the drug and the are the antirenin system drug renin and plasma in renin in to the drug Thus, or to the antirenin of to of the drug are basically V drugs that either primarily or to extracellular and plasma sodium that is the V or sodium volume factor, the cardiac output of the Poiseuille equation. 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The left to the and the BP, that the with an appropriate drug the The arterial vasoconstriction of the hypertension associated with just all primarily mediated by either a sodium volume V excess or by a renin-angiotensin R either of which is by plasma renin testing that values >0.65 renin values to a sodium volume However, the plasma renin test can the of this first of the renin factor using or and is the is or the is and to test and the to or to this if the patient is a or if a is and if necessary, to or or V therapy by the of either or and this therapy is in it be to the V by the or by or a or to the these to be patients with either or are and, just or more can patients with hypertensive present with also with with or more and in by Thus, in this either V depletion or V can be As discussed, is body salt and is an R antirenin the BP can to (see Lesson XIV). This has by of and produce and in with a or an to R when first to treat patients in of patients or when the in full strength to patients. 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This first increases pressure to then, also to sodium and to of the of the Thus, the of both and can be by the heart, by a to the excess These by the of of the first by the by which also and to and best of all by angiotensin to BP and cardiac using one of the R either or a that that an renin-angiotensin system is the factor for and it is how this if to that drug for an individual patient can be mechanistically for by and the either the renin-angiotensin or the sodium volume excess that is primary to the with our important to the of which are to understanding and patients. the in plasma renin values that in or patients. of these data it is that plasma renin values are for the is also in patients plasma levels (PRA <0.65 ng/mL/h). To this studied patients with therapy for to our a low sodium of for by a in salt to for the second in either that the salt a of feeding the plasma renin levels in patients to the low in primary or low renin hypertension. the degree of of these renin and levels with a of sodium and that patients with the renin the the important of this the that this of renin and the peripheral and salt feeding This salt feeding the for the arteriolar vasoconstriction renin mediated to salt mediated when plasma renin levels of promptly by renin Conversely, salt feeding just by the salt body content of by plasma which suppressed that correct this vasoconstriction. This of vasoconstriction to or to or This therefore, in also in normal and hypertensive people (see Lesson and in hypertensive in see the of two of one salt the renin that all normotension or hypertension. in salt an of these volume and vasoconstrictor that salt depletion renin which the sodium low renin vasoconstriction or This of salt and renin-mediated vasoconstriction also in of the a model to (see previous in the of this how the plasma renin-angiotensin factor with the salt to all normotension or hypertension. The model also salt promptly renin to BP control levels and However, this the of sodium volume depletion with to the In these the volume vasoconstriction model (see XIV and XV) is in all of In this context, the close the plasma renin levels in and the of to peripheral and the of in the low renin patients. two one with renin to with a in and pressure and a in cardiac output with of In in the patient with the low renin strength R a of a V promptly a in with a of V and R drugs are when to the V or R of vasoconstriction and are in the of this plasma renin testing is a for and more in more to in the renin value Thus, this these two of vasoconstriction the primary BP either by plasma renin-angiotensin or by salt in the of which in both normal and hypertensive (see XIV and in the hypertension of patients with (see previous and, discussed in this for BP of either hypertensive or pressure levels that in patients with or of of the in the and also that of and of the hypertension model. In all of these renin testing whether hypertension or normotension is primarily in the sodium volume-mediated (PRA <0.65 ng/mL/h) or in the renin-mediated (PRA >0.65 ng/mL/h) to to the in that these vasoconstrictor can also in the two different of In patients with or with hypertension and or all hypertension when salt depletion is which are by increases in plasma renin salt is the hypertension, it is by the sodium volume excess and is by a body sodium volume and The in normal with salt and it also in of the a to (see the correct treatment for the hypertension associated with or with can be with by plasma renin testing to the factor in the hypertension either the sodium volume V mediated (PRA <0.65 ng/mL/h) or the renin R mediated (PRA >0.65 ng/mL/h). Because the renin test is for an drug testing and in which the the renin test to an R and a V drug first in these the plasma renin values for patients an with the in a control an These values in patients an in in the The also that more of the patients values >0.65 Thus, the that of patients values <0.65 ng/mL/h, that renin is in patients and that an is in patients with low renin This plasma renin with an more the of hypertension, or Thus, using a to in or drug use this a levels and in of all of these in the of the the R therapy first is patients an control an and also of the that plasma renin-angiotensin levels to of in both hypertensive and in discussed in these it be a to R therapy for that there a V sodium volume factor, the of which the drug strategy. This is also for the correct hypertensive therapy for patients drugs hypertension is a (see and an be to a patient a R drug has a plasma patients are volume that renin of pressure can the BP to to also the This in of patients and can be by renin testing the use of a test of a R the value of R drugs in the the R drug be the first choice of and cardiac to values to BP, all of which cardiac and cardiac that plasma levels just or more the that the also the of or by plasma renin increases in to Thus, it is for an patient to more one R drug to This to a to which the value of and drugs fit this are and These drugs are that the Thus, 1) the the to the 2) the the that and in this the and by in low renin the in the in patients with and it function the also more in the these a more for the of patients with and for the for patients with In are I can that either or treatment in values the just I