Hypertension is a metabolic disease, a hormonal disease, an endocrinopathy. While various pathophysiological mechanisms have been postulated to explain the occurrence of high blood pressure, there is no unifying hypothesis of hypertension given so far. Yet, as we gain newer insights into the biochemistry and physiology of the human body, it becomes more and more evident that our initial statement is correct: Hypertension is an endocrinopathy.
Blood pressure is necessary to keep the blood moving in the circulatory system and to maintain life. A comparative study of the cardiovascular physiology of various mammalian species reveals that though heart size, heart rate and vascular size/length vary according to the body mass (these are known as scaled variables),[1] blood pressure exhibits virtually no inter-species variability. In spite of gross variation in size, the mean arterial blood pressure (ABP) in the aortic root is similar in all mammals (about 100 mg Hg).
The only exception to this rule is the giraffe, which has evolved to have an elongated neck. To maintain adequate blood flow to the brain, giraffes have developed extremely high blood pressure, with estimates ranging from 180 to 300 mg Hg.[2,3]
In human societies, blood pressure seems to increase with modernization. Even modern day hunter-gatherer tribesmen and women have typical mammalian blood pressure (mean ABP 100 mm Hg), while members of westernized societies have much higher blood pressure. This may be due to increased salt intake, an abnormal ratio, or an imbalance in calorie consumption and expenditure.[4]
While giraffes evolved a hypertensive status to go along with their elongated cervical vertebrae, and to help them survive, it is unclear as to why humans need higher blood pressure. What survival benefits, if any, does hypertension confer on us?
Because of this, and other unanswered questions, the study of hypertension is an exciting one. The undisputed contribution of endocrinology to this field of medicine, however, has been overlooked by medical historians and practitioners alike.
Hypertension texts have tended to highlight contributions related to renal, vascular and cardiac aspects of the disease.[5] Treatises on endocrinology have focused on the development of “classical” endocrinology, dealing with the pituitary, parathyroid, thyroid, pancreas, adrenal, and gonads.[6] This has led to a lack of realization of the importance of endocrinology in hypertension.
The hormonal basis for the development of hypertension is gradually being unraveled, but is far from simple. In 1897, a hormone known as renin was discovered by Tigerstedt and Bergman. This major advance antedated the discovery of most hormones, and hence, its importance may not have been realized by the endocrine community at that time. In 1934, Goldblatt found that renin secretion, and blood pressure, increased following renal artery constriction. Six years later, Page and Helmer, as well as Braun-Menendez, discovered angiotensin, a downstream polypeptide formed by the action of rennin.[5]
These discoveries were not highlighted by endocrinologists, who perhaps were busy with the more exciting hormones and diseases such as insulin and diabetes. This led to a lack of interest in, and poor understanding of, the ill-effects of hypertension. It also delayed the development of hormone-based drugs, the angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and renin inhibitors, by many decades.
Recent developments helped establish the heart as an endocrine organ. De Bold et al. discovered a natriuretic factor in atrial extracts in 1981, which led to the isolation and discovery of atrial natriuretic peptide (ANP; an atrial hormone), B-natriuretic peptide (BNP; a ventricular hormone) and C-natriuretic peptide (CNP; an autocrine/paracrine factor).[7] In the same decade, the 1980s, the vascular endothelium was recognized as the largest endocrine gland. Three members of the endothelin family of 21-amino acid peptides (ET-1, ET-2, and ET-3) were identified by 1989, and ET-1 was understood to be a major hormone regulating blood pressure. In 1993, Kitamura et al. discovered adrenomedullin, a potent vasodepressor peptide, which seems to have autocrine and paracrine, rather than endocrine, effects.[8]
Other hormones involved in the homeostasis of blood pressure include the catecholamines, viz., adrenaline, noradrenaline, and dopamine. Vasodepressor hormones such as kinins, eicosanoids, nitric oxide, and endothelium-derived hyperpolarizing factor (EDHF) also contribute to the homeostasis of blood pressure, albeit in a paracrine manner.[7]
All these hormones are implicated in the pathogenesis of essential hypertension. The discovery of these hormones has contributed, in no small way, to the understanding of hypertension, and has led to the development of drugs for the condition. These “cardiovascular” hormones are as integral a part of endocrinology as the classical gland secretions.
Yet, when we talk of hypertension, we do not think of it as an endocrinopathy. Even if we do so, we consider the secondary causes of hypertension such as pituitary disease, hyperparathyroidism, hypo- and hyperthyroidism, and adrenal hyperfunction as endocrine causes of high blood pressure. The common endocrinopathies associated with hypertension, such as diabetes mellitus, are sometimes omitted from this list. This myopic view point tends to neglect the important role of endocrinology in hypertension.
Over a billion people across the globe suffer from hypertension.[9] The prevalence increases with age, obesity, diabetes lack of physical activity, and with certain diets. Hypertension is a potent risk factor for cardiovascular, peripheral vascular, cerebrovascular, and renal disease. It is an important part of the metabolic syndrome. Keeping this public health impact in mind, it becomes important for endocrinologists to focus on this aspect of cardiovascular endocrinology.
While the Endocrine Society (USA) chose cardiovascular endocrinology as its presidential theme for 2003, not much follow-up was done in this sphere. In the Indian endocrine context too, hypertension specifically, and cardiovascular endocrinology in general, have not been given the attention that they deserve.
This supplement of the IJEM focuses on some of the endocrine aspects of hypertension, as well as on hypertension in some endocrine conditions. The accompanying editorial by Baruah et al.[10] provides a bird's eye view of the scope of this issue. It is hoped that this issue will stimulate discussion on this important endocrinopathy. A concerted effort involving allied specialties such as cardiology, nephrology, and internal medicine will help reduce the burden of this disease, as well as the complications arising out of it. From Darwin to Dawkins, all serious biologists have described natural selection as the sole driving force of adaptive evolution, i.e. evolution toward positive improvement.[11] With the current prevalence of hypertension reaching an epidemic proportion, one can only hope that we humans do not have to evolve into giraffes.