The small arteries play an important functional role in establishing the increased peripheral resistance found in essential hypertension. This paper concerns the direct measurement of the intrinsic mechanical and contractile properites of two categories of small arterial resistance vessels in the mesenteric bed of 5-month-old normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The vessels had mean internal diameters of 246 fim and 153 /*m when relaxed at 100 mm Hg effective transmural pressure. Segments (1 mm) were mounted in such a way that internal circumference could be controlled and the circumferential wall tension (T) measured. After mounting, each vessel was maximally activated (by K* depolarization at 37°C in the presence of 5 mM Ca) at an internal circumference for which AT was approximately maximal, where AT = Tactlve Trelaxed. From the average values of AT measured we have estimated (on the basis of Laplace's equation) that the SHR vessel would average values of AT measured we have estimated (on the basis of Laplace's equation) that the SHR vessels would have been able to contract against 34% greater pressures than the WKY vessels (P < 0.001). Optical measurements of the dimensions of these vessels showed a 23% greater wall thickness in the SHR vessels (P < 0.02). There were no significant differences in the calculated active wall stresses of the SHR and WKY vessels; this suggests that the greater contractility found in the SHR vessels may be due to their having a greater smooth muscle cell content. These vessel measurements have been examined as well as the rats' blood pressures and heart to body weight ratios. The comparison points to the possibility that the disturbance to the cardiovascular regulatory system which results in hypertension produces similar cellular responses in both the myocardium and the peripheral vasculature.

Contractile Properties of Small Arterial Resistance Vessels in Spontaneously Hypertensive and Normotensive Rats

Men are at greater risk for cardiovascular and renal disease than are age-matched, premenopausal women. Recent studies using the technique of 24-hour ambulatory blood pressure monitoring have shown that blood pressure is higher in men than in women at similar ages. After menopause, however, blood pressure increases in women to levels even higher than in men. Hormone replacement therapy in most cases does not significantly reduce blood pressure in postmenopausal women, suggesting that the loss of estrogens may not be the only component involved in the higher blood pressure in women after menopause. In contrast, androgens may decrease only slightly, if at all, in postmenopausal women. In this review the possible mechanisms by which androgens may increase blood pressure are discussed. Findings in animal studies show that there is a blunting of the pressure-natriuresis relationship in male spontaneously hypertensive rats and in ovariectomized female spontaneously hypertensive rats treated chronically with testosterone. The key factor in controlling the pressure-natriuresis relationship is the renin-angiotensin system (RAS). The possibility that androgens increase blood pressure via the RAS is explored, and the possibility that the RAS also promotes oxidative stress leading to production of vasoconstrictor substances and reduction in nitric oxide availability is proposed.

Gender Differences in the Regulation of Blood Pressure

The arterial pressure of the adult human rarely deviates from normal by more than 10 to 15 percent during each day. To achieve such constancy, the body has a network of pressure control systems. Several are based on neural receptors that respond within seconds to help correct any abnormal pressure. The activities of these systems are followed within minutes by activation of hormonal controllers. Within hours or days, a kidney pressure control system is induced that increases body fluid volume when the pressure falls (or decreases the volume when the pressure rises). This kidney-fluid system is the dominant method of establishing long-term pressure control.

https://science.sciencemag.org/content/sci/252/5014/1813.full.pdf

Blood pressure control--special role of the kidneys and body fluids.

https://www.zora.uzh.ch/id/eprint/78860/1/Eckardt_Lancet_2013.pdf

Evolving importance of kidney disease: from subspecialty to global health burden

In salt-sensitive hypertension, the accumulation of Na(+) in tissue has been presumed to be accompanied by a commensurate retention of water to maintain the isotonicity of body fluids We show here that a high-salt diet (HSD) in rats leads to interstitial hypertonic Na(+) accumulation in skin, resulting in increased density and hyperplasia of the lymphcapillary network The mechanisms underlying these effects on lymphatics involve activation of tonicity-responsive enhancer binding protein (TonEBP) in mononuclear phagocyte system (MPS) cells infiltrating the interstitium of the skin TonEBP binds the promoter of the gene encoding vascular endothelial growth factor-C (VEGF-C, encoded by Vegfc) and causes VEGF-C secretion by macrophages MPS cell depletion or VEGF-C trapping by soluble VEGF receptor-3 blocks VEGF-C signaling, augments interstitial hypertonic volume retention, decreases endothelial nitric oxide synthase expression and elevates blood pressure in response to HSD Our data show that TonEBP-VEGF-C signaling in MPS cells is a major determinant of extracellular volume and blood pressure homeostasis and identify VEGFC as an osmosensitive, hypertonicity-driven gene intimately involved in salt-induced hypertension

Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C–dependent buffering mechanism

Arterial pressure regulation: Overriding dominance of the kidneys in long-term regulation and in hypertension☆

Brief Reviews: A Systems Analysis Approach to Understanding Long-Range Arterial Blood Pressure Control and Hypertension

In this paper we have presented briefly three different aspects of arterial pressure regulation and of the hypertension problem: (1) the basic principles of arterial pressure control, progressing from simple, individual regulatory mechanisms to complex interactions between these mechanisms; (2) several systems analyses of arterial pressure regulation and of hypertension, also progressing from simple to complex; and (3) animal and human verification of both the logical principles and the systems analyses.

Systems analysis of arterial pressure regulation and hypertension.

We studied the combined effect of subpressor amounts of angiotensin and long-term sodium chloride infusion on arterial pressure in 16 dogs for periods of 2--8 weeks. In dogs receiving 3.5 liters of isotonic NaCl daily, but no angiotensin, the arterial pressure increased an average of only 3 mm Hg. When angiotensin was infused continuously at a rate of 5 ng/kg per min (a rate too small to cause an observable immediate increase in pressure, subsequent infusion of 3.5 liters of saline daily then increased the pressure by 39 mm Hg. The urinary output of sodium increased to the same extent in both instances, that is, there was no extra sodium loss because of the elevated pressure. This suggests that the angiotensin significantly blocked the normal "pressure natriuresis" usually seen with such large increases in pressure. However, the plasma aldosterone levels during angiotensin infusion were not found to be different from those in the absence of angiotensin. Therefore, we have suggested that the tendency of the kidneys to retain sodium under the influence of angiotensin was probably caused mainly by a direct effect of angiotensin on the kidney itself. Such a direct renal sodium-retaining effect also could be a contributing factor in the marked hypertension that results from salt administration in the presence of small amounts of angiotensin.

Subpressor angiotensin infusion, renal sodium handling, and salt-induced hypertension in the dog.

The steady-state relationship between mean arterial pressure (AP) and output of sodium and water was determined for one-kidney control (1KC), one-kidney Goldblatt (1KG), normotensive Wistar-Kyoto (WKY), and Okamoto spontaneously hypertensive rats (SHR). Control fluid intake (given by intravenous infusion) was set at approximately 30 ml/day Ringer solution. The infusion rate was then increased progressively to 2, 4, and 8 times control for 24- to 48-h periods each. Control AP averaged 115 Torr in 1KC, 152 Torr in 1KG, 120 Torr in WKY, and 158 Torr in SHR. The eightfold increase in salt and water intake was accompanied by almost equal increase in salt and water output and increases in AP to 157 Torr in 1KC, 190 Torr in 1KG, 126 Torr in WKY, and 166 Torr in SHR. The arterial pressure-urinary output relationship in 1KG is parallel to that of 1KC but shifted to higher AP levels. Similarly, this relationship in SHR is parallel to that of WKY but shifted to higher AP levels. This parallel shift is indicative of uniform renal vasoconstriction but normal functional renal mass in the SHR.

R. A. Norman

Papers

Arterial pressure regulation: Overriding dominance of the kidneys in long-term regulation and in hypertension☆

Brief Reviews: A Systems Analysis Approach to Understanding Long-Range Arterial Blood Pressure Control and Hypertension

Systems analysis of arterial pressure regulation and hypertension.

Subpressor angiotensin infusion, renal sodium handling, and salt-induced hypertension in the dog.

Arterial pressure-urinary output relationship in hypertensive rats