IN 1963, Okamoto and Aoki introduced a new model of experimental hypertension that required no physiological, pharmacological, or surgical intervention. This spontaneously hypertensive rat (SHR) was developed by meticulous genetic (brother-to-sister) inbreeding that uniformly resulted in 100% of the progeny having naturally occurring hypertensive disease (Okamoto and Aoki, 1963; Okamoto et al., 1966a). Since then, several expert panels have reported that the SHR is an excellent model of experimental hypertension that could serve as a counterpart for clinical essential hypertension (Undenfriend and Spector, 1972; ILAR, 1976). In this discourse we take the affirmative position that the SHR is, indeed, an excellent model for the study of essential hypertension. We do so, however, with four important caveats. First, we recognize that it is unlikely that both forms of naturally occurring hypertension (man and rat) are identical expressions of genetically determined hypertensive disease. Second, we take the position that both forms of hypertension are polygenic in origin and that both are influenced by environmental factors. Thirdly, since the control of normal arterial pressure in both man and rat is multifactorial, it follows that certain pressor mechanisms might well operate in one form of genetic hypertension that do not necessarily occur in the other (although in both, some similar factors could be involved). This same reasoning also may be applied to hypertensive in-

Similarities of genetic (spontaneous) hypertension. Man and rat.

Functions of the renal nerves.

An absolute, supraphysiologic elevation in GFR is observed early in the natural history in 10%-67% and 6%-73% of patients with type 1 and type 2 diabetes, respectively. Moreover, at the single-nephron level, diabetes-related renal hemodynamic alterations-as an adaptation to reduction in functional nephron mass and/or in response to prevailing metabolic and (neuro)hormonal stimuli-increase glomerular hydraulic pressure and transcapillary convective flux of ultrafiltrate and macromolecules. This phenomenon, known as glomerular hyperfiltration, classically has been hypothesized to predispose to irreversible nephron damage, thereby contributing to initiation and progression of kidney disease in diabetes. However, dedicated studies with appropriate diagnostic measures and clinically relevant end points are warranted to confirm this assumption. In this review, we summarize the hitherto proposed mechanisms involved in diabetic hyperfiltration, focusing on ultrastructural, vascular, and tubular factors. Furthermore, we review available evidence on the clinical significance of hyperfiltration in diabetes and discuss currently available and emerging interventions that may attenuate this renal hemodynamic abnormality. The revived interest in glomerular hyperfiltration as a prognostic and pathophysiologic factor in diabetes may lead to improved and timely detection of (progressive) kidney disease, and could provide new therapeutic opportunities in alleviating the renal burden in this population.

/pdf/glomerular-hyperfiltration-in-diabetes-mechanisms-clinical-3501d774sp.pdf

Glomerular Hyperfiltration in Diabetes: Mechanisms, Clinical Significance, and Treatment

The functions of the renal nerves

The mechanisms responsible for the increase in blood pressure response to high salt intake in salt-sensitive patients with essential hypertension are complex and only partially understood. A complex interaction between neuroendocrine factors and the kidney may underlie the propensity for such patients to retain salt and develop salt-dependent hypertension. The possible role of vasodilator and natriuretic agents, such as the prostaglandins, endothelium-derived relaxing factor, atrial natriuretic factor, and kinin-kallikrein system, requires further investigation. An association between salt sensitivity and a greater propensity to develop renal failure has been described in certain groups of hypertensive patients, such as blacks, the elderly, and those with diabetes mellitus. Salt-sensitive patients with essential hypertension manifest a deranged renal hemodynamic adaptation to a high dietary salt intake. During a low salt diet, salt-sensitive and salt-resistant patients have similar mean arterial pressure, glomerular filtration rate, effective renal plasma flow, and filtration fraction. On the other hand, during a high salt intake glomerular filtration rate does not change in either group, and effective renal blood flow increases in salt-resistant but decreases in salt-sensitive patients; filtration fraction and glomerular capillary pressure decrease in salt-resistant but increase in salt-sensitive patients. Salt-sensitive patients are also more likely than salt-resistant patients to manifest left ventricular hypertrophy, microalbuminuria, and metabolic abnormalities that may predispose them to cardiovascular diseases. In conclusion, salt sensitivity in hypertension is associated with substantial renal, hemodynamic, and metabolic abnormalities that may enhance the risk of cardiovascular and renal morbidity.

Salt sensitivity in hypertension. Renal and cardiovascular implications.

/pdf/evaluation-of-renal-resistances-with-special-reference-to-16hclqpbom.pdf

Domingo M. Gómez

Papers

Evaluation of renal resistances, with special reference to changes in essential hypertension