Hypertension is a prevalent condition in the developed world and disease severity is directly correlated with additional cardiovascular complications. It is estimated that 30% of the adult population in the United States has hypertension, which is classified as a systolic blood pressure ≥140 mmHg and/or a diastolic blood pressure ≥90 mmHg. A prolonged increase in afterload ultimately leads to congestive heart failure in the majority of cases. Currently, medication designed to treat hypertension is inadequate, thus new therapies need to be explored. Blood pressure is tightly regulated by blood vessel radius, which is established by hormones and/or peptides binding to GPCRs (G-protein-coupled receptors). Catecholamines and peptide hormones, such as AngII (angiotensin II), are elevated in hypertension and, therefore, signalling by these GPCRs is increased. Their signalling is tightly controlled by a class of proteins, the GRKs (GPCR kinases). Elevated levels of either GRK2 or GRK5 in both the lymphocytes and VSM (vascular smooth muscle) are associated with human hypertension and animal models of the disease. The focus of the present review is on the role GRKs, and their regulation of GPCRs, play in high blood pressure.
1. The pulsatile nature of luteinizing hormone (LH) secretion has recognized physiological and clinical importance, but because of the difficulties with statistical analysis of serial data the precise nature of this pulsed signal is poorly understood. Several groups have noted small-amplitude, high-frequency pulses superimposed on large slower pulses, but, using conventional methods of analysis, it is not possible to distinguish these from assay variation or to characterize them. 2. In an alternative approach we have applied the methods of time series analysis which identify the harmonic patterns within data. Twenty-four healthy women in the early follicular phase of the cycle had blood samples taken at intervals of 1, 5 or 10 min for up to 6 h. 3. We found that LH secretion consists of superimposed harmonics of varying amplitude which occur in frequency bands of about (a) 1–3 h and (b) 2–3 min. Investigations excluded a reproducible pulsatility in our LH assay, implying that the small fast pulses are physiological events. 4. We conclude that LH release is highly complex and that the methods of time series analysis permit identification and characterization of the multiple pulses.